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The role of Na,K‑ATPase in lung diseases (Review)

  • Authors:
    • Zhenyu Liu
    • Tingyan Dong
    • Fei Li
    • Chunmei He
    • Weizhen Zhang
    • Biyun Li
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Shenzhen Nanshan People's Hospital, Shenzhen, Guangdong 518000, P.R. China, Integrated Diagnostic Centre for Infectious Diseases, Guangzhou Hua Yin Medical Laboratory Center, Guangzhou, Guangdong 511400, P.R. China, Department of Pharmacy, The Second People's Hospital of Futian District, Shenzhen, Guangdong 518048, P.R. China, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 300
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    Published online on: August 27, 2025
       https://doi.org/10.3892/mmr.2025.13665
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Abstract

Na,K‑ATPase, commonly referred to as the sodium pump, is known for its essential function as an ion pump, which is key for transporting Na+ and K+ across plasma cell membranes. Additionally, Na,K‑ATPase has multiple biological functions, independent of ion pumping, which are involved in regulating cell proliferation, apoptosis, differentiation and other processes associated with the development and progression of various diseases; particularly cancer, cardiovascular diseases, nervous system diseases, kidney diseases and lung diseases. As a potential therapeutic target, Na,K‑ATPase may represent a novel strategy for treating these diseases in the future. The present review aims to summarize the role of Na,K‑ATPase in lung diseases.
View Figures

Figure 1

Schematic illustration of
Na+/K+−ATPase signaling pathway.
Na+/K+−ATPase acts as an ion pump and signal
transducer, triggering lung inflammation. The binding of ouabain to
Na+/K+−ATPase signalosome located in caveolae
transduces signals to multiple pathways. Ouabain binding to the
Na+/K+-ATPase activates Src and PLC which, in
turn, evokes transactivation of EGFR and, together with the
recruitment of adaptor proteins and Ras, leads to the activation of
Ras-Raf-MAPK/ERK1/2 signaling pathway and intracellular
Ca2+ waves. Ras-Raf-MAPK/ERK1/2 signaling pathway can
activate NF-κB. NF-κB activation by ouabain induces the expression
of pro-inflammatory genes. The activation of the Ras-Raf-MAPK
cascade reaction triggers mitochondria to produce ROS. The
activation of ROS and enhanced Ca2+ activates NF-κB,
leading to the activation of the immune system, cell proliferation
and apoptosis. Ouabain can also induce the physical interaction
between Na+/K+−ATPase and inositol
triphosphate receptor, triggering intracellular Ca2+
waves. Moreover, the binding of ouabain to
Na+/K+−ATPase also stimulates PI3K. ROS
release stimulates AKT and NF-κB activation. AKT can activate PI3K
and NF-κB or be phosphorylated by PI3K, essential to inflammation.
However, the type of reaction depends on the cell type, glycoside
concentration and exposure time. Src, non-receptor tyrosine
kinases; PLC, phospholipase C; ROS, reactive oxygen species; PIP,
phosphatidylinositol (3,4,5)-trisphosphate.
View References

1 

Skou JC: The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim Biophys Acta. 23:394–401. 1957. View Article : Google Scholar : PubMed/NCBI

2 

Kaplan JH: Biochemistry of Na,K-ATPase. Annu Rev Biochem. 71:511–535. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Mobasheri A, Avila J, Cózar-Castellano I, Brownleader MD, Trevan M, Francis MJ, Lamb JF and Martín-Vasallo P: Na+, K+-ATPase isozyme diversity; comparative biochemistry and physiological implications of novel functional interactions. Biosci Rep. 20:51–91. 2000. View Article : Google Scholar : PubMed/NCBI

4 

Rajasekaran SA, Gopal J, Willis D, Espineda C, Twiss JL and Rajasekaran AK: Na,K-ATPase beta1-subunit increases the translation efficiency of the alpha1-subunit in MSV-MDCK cells. Mol Biol Cell. 15:3224–3232. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Blanco G, Sánchez G and Mercer RW: Differential regulation of Na,K-ATPase isozymes by protein kinases and arachidonic acid. Arch Biochem Biophys. 359:139–150. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Benarroch EE: Na+, K+-ATPase: Functions in the nervous system and involvement in neurologic disease. Neurology. 76:287–293. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Lemas MV, Hamrick M, Takeyasu K and Fambrough DM: 26 Amino acids of an extracellular domain of the Na,K-ATPase alpha-subunit are sufficient for assembly with the Na,K-ATPase beta-subunit. J Biol Chem. 269:8255–8259. 1994. View Article : Google Scholar : PubMed/NCBI

8 

Geering K, Meyer DI, Paccolat MP, Kraehenbühl JP and Rossier BC: Membrane insertion of alpha- and beta-subunits of Na+,K+-ATPase. J Biol Chem. 260:5154–5160. 1985. View Article : Google Scholar : PubMed/NCBI

9 

Blanco G: Na,K-ATPase subunit heterogeneity as a mechanism for tissue-specific ion regulation. Semin Nephrol. 25:292–303. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Geering K: Functional roles of Na,K-ATPase subunits. Curr Opin Nephrol Hypertens. 17:526–532. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Geering K: FXYD proteins: new regulators of Na-K-ATPase. Am J Physiol Renal Physiol. 290:F241–F250. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Contreras RG, Torres-Carrillo A, Flores-Maldonado C, Shoshani L and Ponce A: Na+/K+-ATPase: More than an electrogenic pump. Int J Mol Sci. 25:61222024. View Article : Google Scholar : PubMed/NCBI

13 

Laursen M, Gregersen JL, Yatime L, Nissen P and Fedosova UN: Structures and characterization of digoxin- and bufalin-bound Na+,K+-ATPase compared with the ouabain-bound complex. Proc Natl Acad Sci USA. 112:1755–1760. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Quintas LE, Pierre SV, Liu LJ, Bai Y, Liu XC and Xie ZJ: Alterations of Na+/K+-ATPase function in caveolin-1 knockout cardiac fibroblasts. J Mol Cell Cardiol. 49:525–531. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Skou JC: The identification of the sodium pump. Biosci Rep. 24:436–451. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Xie ZJ and Askari A: Na(+)/K(+)-ATPase as a signal transducer. Eur J Biochem. 269:2434–2439. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Pierre SV and Xie Z: The Na,K-ATPase receptor complex: Its organization and membership. Cell Biochem Biophys. 46:303–316. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Rajasekaran SA and Rajasekaran AK: Na,K-ATPase and epithelial tight junctions. Front Biosci (Landmark Ed). 14:2130–2148. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Barwe SP, Anikmar G, Moon SY, Zeng Y, Whitelegge JP, Rajasekaran SA and Rajasekaran AK: Novel role for Na,K-ATPase in phosphatidylinositol 3-kinase signaling and suppression of cell motility. Mol Biol Cell. 16:1082–1094. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Kimura T, Han W, Pagel P, Nairn AC and Caplan MJ: Protein phosphatase 2A interacts with the Na,K-ATPase and modulates its trafficking by inhibition of its association with arrestin. PLoS One. 6:e292692011. View Article : Google Scholar : PubMed/NCBI

21 

Ren Y, Anderson AT, Meyer G, Lauber KM, Gallucci JC and Douglas Kinghorn A: Digoxin and its Na+/K+-ATPase-targeted actions on cardiovascular diseases and cancer. Bioorg Med Chem. 114:1179392024. View Article : Google Scholar : PubMed/NCBI

22 

Maxwell KD, Chuang J, Chaudhry M, Nie Y, Bai F, Sodhi K, Liu J and Shapiro JI: The potential role of Na-K-ATPase and its signaling in the development of anemia in chronic kidney disease. Am J Physiol Renal Physiol. 320:F234–F242. 2021. View Article : Google Scholar : PubMed/NCBI

23 

Bartlett DE, Miller RB, Thiesfeldt S, Lakhani HV, Shapiro JI and Sodhi K: The role of Na/K-ATPase signaling in oxidative stress related to aging: Implications in obesity and cardiovascular disease. Int J Mol Sci. 19:21392018. View Article : Google Scholar : PubMed/NCBI

24 

Thai AA, Solomon BJ, Sequist LV, Gainor JF and Heist RE: Lung cancer. Lancet. 398:535–554. 2021. View Article : Google Scholar : PubMed/NCBI

25 

Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL and Paz-Ares L: Lung cancer: Current therapies and new targeted treatments. Lancet. 389:299–311. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Luo G, Zhang Y, Rumgay H, Morgan E, Langselius O, Vignat J, Colombet M and Bray F: Estimated worldwide variation and trends in incidence of lung cancer by histological subtype in 2022 and over time: A population-based study. Lancet Respir Med. 13:348–363. 2025. View Article : Google Scholar : PubMed/NCBI

27 

Hirsch FR, Suda K, Wiens J and Bunn PA Jr: New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 388:1012–1024. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Stenkvist B, Bengtssion E, Dahlqvist B, Eriksson O, Jarkrans T and Nordin B: Cardiac glycosides and breast cancer, revisited. N Engl J Med. 306:4841982. View Article : Google Scholar : PubMed/NCBI

29 

Siegel RL, Giaquinto AN and Jemal A: Cancer statistics, 2024. CA Cancer J Clin. 74:12–49. 2024.PubMed/NCBI

30 

Felippe Gonçalves-de-Albuquerque C, Ribeiro Silva A, Ignácio da Silva C, Caire Castro-Faria-Neto H and Burth P: Na/K pump and beyond: Na/K-ATPase as a modulator of apoptosis and autophagy. Molecules. 22:5782017. View Article : Google Scholar : PubMed/NCBI

31 

Bejček J, Spiwok V, Kmoníčková E and Rimpelová S: Na+/K+-ATPase revisited: On its mechanism of action, role in cancer, and activity modulation. Molecules. 26:19052021. View Article : Google Scholar : PubMed/NCBI

32 

Diederich M, Muller F and Cerella C: Cardiac glycosides: From molecular targets to immunogenic cell death. Biochem Pharmacol. 125:1–11. 2017. View Article : Google Scholar : PubMed/NCBI

33 

Huynh TP, Mah V, Sampson VB, Chia D, Fishbein MC, Horvath S, Alavi M, Wu DC, Harper J, Sarafian T, et al: Na,K-ATPase is a target of cigarette smoke and reduced expression predicts poor patient outcome of smokers with lung cancer. Am J Physiol Lung Cell Mol Physiol. 302:L1150–L1158. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Schneider C, Spaink H, Alexe G, Dharia NV, Meyer A, Merickel LA, Khalid D, Scheich S, Häupl B, Staudt LM, et al: Targeting the sodium-potassium pump as a therapeutic strategy in acute myeloid leukemia. Cancer Res. 84:3354–3370. 2024. View Article : Google Scholar : PubMed/NCBI

35 

Espineda C, Seligson DB, Ball WJ Jr, Rao JY, Palotie A, Horvath S, Huang Y, Shi T and Rajasekaran AK: Analysis of the Na,K-ATPase alpha- and beta-subunit expression profiles of bladder cancer using tissue microarrays. Cancer. 97:1859–1868. 2003. View Article : Google Scholar : PubMed/NCBI

36 

Rajasekaran SA, Ball WJ Jr, Bander NH, Liu H, Pardee JD and Rajasekaran AK: Reduced expression of beta-subunit of Na,K-ATPase in human clear-cell renal cell carcinoma. J Urol. 162:574–580. 1999. View Article : Google Scholar : PubMed/NCBI

37 

Rajasekaran SA, Huynh TP, Wolle DG, Espineda CE, Inge LJ, Skay A, Lassman C, Nicholas SB, Harper JF, Reeves AE, et al: Na,K-ATPase subunits as markers for epithelial-mesenchymal transition in cancer and fibrosis. Mol Cancer Ther. 9:1515–1524. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Rajasekaran SA, Palmer LG, Moon SY, Soler AP, Apodaca GL, Harper JF, Zheng Y and Rajasekaran AK: Na,K-ATPase activity is required for formation of tight junctions, desmosomes, and induction of polarity in epithelial cells. Mol Biol Cell. 12:3717–3732. 2001. View Article : Google Scholar : PubMed/NCBI

39 

Barwe SP, Kim S, Rajasekaran SA, Bowie JU and Rajasekaran KA: Janus model of the Na,K-ATPase beta-subunit transmembrane domain: Distinct faces mediate alpha/beta assembly and beta-beta homo-oligomerization. J Mol Biol. 365:706–714. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Inge LJ, Rajasekaran SA, Yoshimoto K, Mischel PS, McBride W, Landaw E and Rajasekaran KA: Evidence for a potential tumor suppressor role for the Na,K-ATPase beta1-subunit. Histol Histopathol. 23:459–467. 2008.PubMed/NCBI

41 

Shoshani L, Contreras RG, Roldán ML, Moreno J, Lázaro A, Balda MS, Matter K and Cereijido M: The polarized expression of Na+,K+-ATPase in epithelia depends on the association between beta-subunits located in neighboring cells. Mol Biol Cell. 16:1071–1081. 2005. View Article : Google Scholar : PubMed/NCBI

42 

Vagin O, Tokhtaeva E and Sachs G: The role of the beta1 subunit of the Na,K-ATPase and its glycosylation in cell-cell adhesion. J Biol Chem. 281:39573–39587. 2006. View Article : Google Scholar : PubMed/NCBI

43 

Udoh UaS, Banerjee M, Rajan PK, Sanabria JD, Smith G, Schade M, Sanabria JA, Nakafuku Y, Sodhi K, Pierre SV, et al: Tumor-suppressor role of the α1-Na/K-ATPase signalosome in NASH related hepatocellular carcinoma. Int J Mol Sci. 23:73592022. View Article : Google Scholar : PubMed/NCBI

44 

Mijatovic T, Roland I, Quaquebeke EV, Nilsson B, Mathieu A, Vynckt FV, Darro F, Blanco G, Facchini V and Kiss R: The alpha1 subunit of the sodium pump could represent a novel target to combat non-small cell lung cancers. J Pathol. 212:170–179. 2007. View Article : Google Scholar : PubMed/NCBI

45 

Liu CC, Kim YJ, Teh R, Garcia A, Hamilton EJ, Cornelius F, Baxter RC and Rasmussen HH: Displacement of native FXYD protein from Na+/K+-ATPase with novel FXYD peptide derivatives: Effects on doxorubicin cytotoxicity. Front Oncol. 12:8592162022. View Article : Google Scholar : PubMed/NCBI

46 

Liu CC, Teh R, Mozar CA, Baxter RC and Rasmussen HH: Silencing overexpression of FXYD3 protein in breast cancer cells amplifies effects of doxorubicin and γ-radiation on Na(+)/K(+)-ATPase and cell survival. Breast Cancer Res Treat. 155:203–213. 2016. View Article : Google Scholar : PubMed/NCBI

47 

Cordeiro BM, Leite Fontes CF and Meyer-Fernandes JR: Molecular basis of Na, K-ATPase regulation of diseases: Hormone and FXYD2 interactions. Int J Mol Sci. 25:133982024. View Article : Google Scholar : PubMed/NCBI

48 

Okudela K, Yazawa T, Ishii J, Woo T, Mitsui H, Bunai T, Sakaeda M, Shimoyamada H, Sato H, Tajiri M, et al: Down-regulation of FXYD3 expression in human lung cancers: Its mechanism and potential role in carcinogenesis. Am J Pathol. 175:2646–2656. 2009. View Article : Google Scholar : PubMed/NCBI

49 

Liu J, Feng Y, Zeng X, He M, Gong Y and Liu Y: Extracellular vesicles-encapsulated let-7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis. J Cell Mol Med. 25:1911–1926. 2021. View Article : Google Scholar : PubMed/NCBI

50 

Crambert G, Li C, Claeys D and Geering K: FXYD3 (Mat-8), a new regulator of Na,K-ATPase. Mol Biol Cell. 16:2363–2371. 2005. View Article : Google Scholar : PubMed/NCBI

51 

Glaviano A, Foo ASC, Lam HY, Yap KCH, Jacot W, Jones RH, Eng H, Nair MG, Makvandi P, Geoerger B, et al: PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer. 22:1382023. View Article : Google Scholar : PubMed/NCBI

52 

LoPiccolo J, Blumenthal GM, Bernstein WB and Dennis PA: Targeting the PI3K/Akt/mTOR pathway: Effective combinations and clinical considerations. Drug Resist Updat. 11:32–50. 2008. View Article : Google Scholar : PubMed/NCBI

53 

Ren Y, Wu S, Burdette JE, Cheng X and Kinghorn AD: Structural insights into the interactions of digoxin and Na+/K+-ATPase and other targets for the inhibition of cancer cell proliferation. Molecules. 26:36722021. View Article : Google Scholar : PubMed/NCBI

54 

Zhu Z, Sun H, Ma G, Wang Z, Li E and Liu Y and Liu Y: Bufalin induces lung cancer cell apoptosis via the inhibition of PI3K/Akt pathway. Int J Mol Sci. 13:2025–2035. 2012. View Article : Google Scholar : PubMed/NCBI

55 

Chanvorachote P and Pongrakhananon V: Ouabain downregulates Mcl-1 and sensitizes lung cancer cells to TRAIL-induced apoptosis. Am J Physiol Cell Physiol. 304:C263–C272. 2013. View Article : Google Scholar : PubMed/NCBI

56 

Yang K, Li Z, Chen Y, Yin F, Ji X, Zhou J, Li X, Zeng T, Fei C, Ren C, et al: Na, K-ATPase α1 cooperates with its endogenous ligand to reprogram immune microenvironment of lung carcinoma and promotes immune escape. Sci Adv. 9:eade53932023. View Article : Google Scholar : PubMed/NCBI

57 

Song X, Xie L, Wang X, Zeng Q, Chen TC, Wang W and Song X: Temozolomide-perillyl alcohol conjugate induced reactive oxygen species accumulation contributes to its cytotoxicity against non-small cell lung cancer. Sci Rep. 6:227622016. View Article : Google Scholar : PubMed/NCBI

58 

Lauf PK, Alqahtani T, Flues K, Meller L and Adragna NC: Interaction between Na-K-ATPase and Bcl-2 proteins BclXL and Bak. Am J Physiol Cell Physiol. 308:C51–C60. 2015. View Article : Google Scholar : PubMed/NCBI

59 

Sun J, Chen L, Jiang P, Duan B, Wang R, Xu J, Liu W, Xu Y, Xie Z, Feng F and Qu W: Phenylethanoid glycosides of Callicarpa kwangtungensis Chun exert cardioprotective effect by weakening Na+-K+-ATPase/Src/ERK1/2 pathway and inhibiting apoptosis mediated by oxidative stress and inflammation. J Ethnopharmacol. 258:1128812020. View Article : Google Scholar : PubMed/NCBI

60 

Wang Z, Pei S, Cui H, Zhang J and Jia Z: Zoonotic spillover and extreme weather events drive the global outbreaks of airborne viral emerging infectious diseases. J Med Virol. 96:e297372024. View Article : Google Scholar : PubMed/NCBI

61 

Majumder J and Minko T: Recent developments on therapeutic and diagnostic approaches for COVID-19. AAPS J. 23:142021. View Article : Google Scholar : PubMed/NCBI

62 

Ochani R, Asad A, Yasmin F, Shaikh S, Khalid H, Batra S, Sohail MR, Mahmood SF, Ochani R, Hussham Arshad M, et al: COVID-19 pandemic: From origins to outcomes. A comprehensive review of viral pathogenesis, clinical manifestations, diagnostic evaluation, and management. Infez Med. 29:20–36. 2021.PubMed/NCBI

63 

Nyachoti DO, Fwelo P, Springer AE and Kelder SH: Association between gross national income per capita and COVID-19 vaccination coverage: A global ecological study. BMC Public Health. 23:24152023. View Article : Google Scholar : PubMed/NCBI

64 

de Wit E, van Doremalen N, Falzarano D and Munster VJ: SARS and MERS: Recent insights into emerging coronaviruses. Nat Rev Microbiol. 14:523–534. 2016. View Article : Google Scholar : PubMed/NCBI

65 

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, et al: Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 382:1708–1720. 2020. View Article : Google Scholar : PubMed/NCBI

66 

Vitalii K and István V: Molecular mechanisms of Na,K-ATPase dysregulation driving alveolar epithelial barrier failure in severe COVID-19. Am J Physiol Lung Cell Mol Physiol. 320:L1186–L1193. 2021. View Article : Google Scholar : PubMed/NCBI

67 

Souza E, Souza KFC, Moraes BPT, Paixão ICNP, Burth P, Silva AR and Gonçalves-de-Albuquerque CF: Na+/K+-ATPase as a target of cardiac glycosides for the treatment of SARS-CoV-2 infection. Front Pharmacol. 12:6247042021. View Article : Google Scholar : PubMed/NCBI

68 

Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, Jordan TX, Oishi K, Panis M, Sachs D, et al: Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 181:1036–1045.e9. 2020. View Article : Google Scholar : PubMed/NCBI

69 

Chen F, Zhang Y, Sucgang R, Ramani S, Corry D, Kheradmand F and Creighton CJ: Meta-analysis of host transcriptional responses to SARS-CoV-2 infection reveals their manifestation in human tumors. Sci Rep. 11:24592021. View Article : Google Scholar : PubMed/NCBI

70 

Ambade V and Ambade S: SARS-CoV-2 infecting endothelial cells, biochemical alterations, autopsy findings and outcomes in COVID-19, suggest role of hypoxia-inducible factor-1. J Med Biochem. 41:14–20. 2022. View Article : Google Scholar : PubMed/NCBI

71 

Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ and van Goor H: Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 203:631–637. 2004. View Article : Google Scholar : PubMed/NCBI

72 

Xie ZJ, Novograd J, Itzkowitz Y, Sher A, Buchen YD, Sodhi K, Abraham NG and Shapiro JI: The pivotal role of adipocyte-Na K peptide in reversing systemic inflammation in obesity and COVID-19 in the development of heart failure. Antioxidants (Basel). 9:11292020. View Article : Google Scholar : PubMed/NCBI

73 

Li F, Li J, Wang PH, Yang N, Huang J, Ou J, Xu T, Zhao X, Liu T, Huang X, et al: SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling. Biochim Biophys Acta Mol Basis Dis. 1867:1662602021. View Article : Google Scholar : PubMed/NCBI

74 

Basile MS, Cavalli E, McCubrey J, Hernández-Bello J, Muñoz-Valle JF, Fagone P and Nicoletti F: The PI3K/Akt/mTOR pathway: A potential pharmacological target in COVID-19. Drug Discov Today. 27:848–856. 2022. View Article : Google Scholar : PubMed/NCBI

75 

Semenza GL: Hypoxia-inducible factors in physiology and medicine. Cell. 148:399–408. 2012. View Article : Google Scholar : PubMed/NCBI

76 

Zhang H, Qian DZ, Tan YS, Lee K, Gao P, Ren YR, Rey S, Hammers H, Chang D, Pili R, et al: Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci USA. 105:19579–19586. 2008. View Article : Google Scholar : PubMed/NCBI

77 

Ha DP, Shin WJ, Liu Z, Doche MiE, Lau R, Leli NM, Conn CS, Russo M, Lorenzato A, Koumenis C, et al: Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19. Cell Biosci. 14:1152024. View Article : Google Scholar : PubMed/NCBI

78 

Newman RA, Sastry KJ, Arav-Boger R, Cai H, Matos R and Harrod R: Antiviral effects of oleandrin. J Exp Pharmacol. 12:503–515. 2020. View Article : Google Scholar : PubMed/NCBI

79 

Van Kanegan MJ, Dunn DE, Kaltenbach LS, Shah B, He DN, McCoy DD, Yang PY, Peng JN, Shen L, Du L, et al: Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke. Sci Rep. 6:256262016. View Article : Google Scholar : PubMed/NCBI

80 

RECOVERY Collaborative Group and Horby P, ; Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, et al: Dexamethasone in hospitalized patients with Covid-19-preliminary report. N Engl J Med. 384:693–704. 2021. View Article : Google Scholar : PubMed/NCBI

81 

Devarajan P and Benz EJ Jr: Translational regulation of Na-K-ATPase subunit mRNAs by glucocorticoids. Am J Physiol Renal Physiol. 279:F1132–F1138. 2000. View Article : Google Scholar : PubMed/NCBI

82 

Matthay MA, Arabi Y, Arroliga AC, Bernard G, Bersten AD, Brochard LJ, Calfee CS, Combes A, Daniel BM, Ferguson ND, et al: A new global definition of acute respiratory distress syndrome. Am J Respir Crit Care Med. 209:37–47. 2024. View Article : Google Scholar : PubMed/NCBI

83 

Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, Herridge M, Randolph AG and Calfee CS: Acute respiratory distress syndrome. Nat Rev Dis Primers. 5:182019. View Article : Google Scholar : PubMed/NCBI

84 

Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, LeGall JR, Morris A and Spragg R: Report of the American-European consensus conference on ARDS: Definitions, mechanisms, relevant outcomes and clinical trial coordination. The consensus committee. Intensive Care Med. 20:225–232. 1994. View Article : Google Scholar : PubMed/NCBI

85 

ARDS Definition Task Force, . Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L and Slutsky AS: Acute respiratory distress syndrome: The Berlin definition. JAMA. 307:2526–2533. 2012.PubMed/NCBI

86 

Hu Q, Zhang S, Yang Y, Yao JQ, Tang WF, Lyon CJ, Hu TY and Wan MH: Extracellular vesicles in the pathogenesis and treatment of acute lung injury. Mil Med Res. 9:612022.PubMed/NCBI

87 

Meyer NJ, Gattinoni L and Calfee CS: Acute respiratory distress syndrome. Lancet. 398:622–637. 2021. View Article : Google Scholar : PubMed/NCBI

88 

Herold S, Gabrielli NM and Vadász I: Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction. Am J Physiol Lung Cell Mol Physiol. 305:L665–L681. 2013. View Article : Google Scholar : PubMed/NCBI

89 

Matthay MA, Folkesson HG and Clerici C: Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Rev. 82:569–600. 2002. View Article : Google Scholar : PubMed/NCBI

90 

Gusarova GA, Trejo HE, Dada LA, Briva A, Welch LC, Hamanaka RB, Mutlu GM, Chandel NS, Prakriya M and Sznajder JI: Hypoxia leads to Na,K-ATPase downregulation via Ca(2+) release-activated Ca(2+) channels and AMPK activation. Mol Cell Biol. 31:3546–3556. 2011. View Article : Google Scholar : PubMed/NCBI

91 

Berger G, Guetta J, Klorin G, Badarneh R, Braun E, Brod V, Saleh NA, Katz A, Bitterman H and Azzam ZS: Sepsis impairs alveolar epithelial function by downregulating Na-K-ATPase pump. Am J Physiol Lung Cell Mol Physiol. 301:L23–L30. 2011. View Article : Google Scholar : PubMed/NCBI

92 

Peteranderl C, Morales-Nebreda L, Selvakumar B, Lecuona E, Vadász I, Morty RE, Schmoldt C, Bespalowa J, Wolff T, Pleschka S, et al: Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection. J Clin Invest. 126:1566–1580. 2016. View Article : Google Scholar : PubMed/NCBI

93 

Gonçalves-de-Albuquerque CF, Silva AR, Burth P, Castro-Faria MV and Castro-Faria-Neto HC: Acute Respiratory Distress Syndrome: Role of oleic acid-triggered lung injury and inflammation. Mediators Inflamm. 2015:2604652015. View Article : Google Scholar : PubMed/NCBI

94 

Gonçalves-de-Albuquerque CF, Burth P, Silva AR, de Moraes IM, de Jesus Oliveira FM, Santelli RE, Freire AS, Bozza PT, Younes-Ibrahim M and de Castro-Faria MV: Oleic acid inhibits lung Na/K-ATPase in mice and induces injury with lipid body formation in leukocytes and eicosanoid production. J Inflamm (Lond). 10:342013. View Article : Google Scholar : PubMed/NCBI

95 

Silva AR, de Souza E Souza KFC, Souza TB, Younes-Ibrahim M, Burth P, de Castro Faria Neto HC and Gonçalves-de-Albuquerque CF: The Na/K-ATPase role as a signal transducer in lung inflammation. Front Immunol. 14:12875122024. View Article : Google Scholar : PubMed/NCBI

96 

Lei J and Ingbar DH: Src kinase integrates PI3K/Akt and MAPK/ERK1/2 pathways in T3-induced Na-K-ATPase activity in adult rat alveolar cells. Am J Physiol Lung Cell Mol Physiol. 301:L765–L771. 2011. View Article : Google Scholar : PubMed/NCBI

97 

Upadhyay D, Lecuona E, Comellas A, Kamp DW and Sznajder JI: Fibroblast growth factor-10 upregulates Na,K-ATPase via the MAPK pathway. FEBS Lett. 545:173–176. 2003. View Article : Google Scholar : PubMed/NCBI

98 

Wang Q, Yan SF, Hao Y and Jin SW: Specialized pro-resolving mediators regulate alveolar fluid clearance during acute respiratory distress syndrome. Chin Med J (Engl). 131:982–989. 2018. View Article : Google Scholar : PubMed/NCBI

99 

Zhang JL, Zhuo XJ, Lin J, Luo LC, Ying WY, Xie X, Zhang HW, Yang JX, Li D, Smith FG and Jin SW: Maresin1 stimulates alveolar fluid clearance through the alveolar epithelial sodium channel Na,K-ATPase via the ALX/PI3K/Nedd4-2 pathway. Lab Invest. 97:543–554. 2017. View Article : Google Scholar : PubMed/NCBI

100 

Yang Q, Xu HR, Xiang SY, Zhang C, Ye Y, Shen CX, Mei HX, Zhang PH, Ma HY, Zheng SX, et al: Resolvin conjugates in tissue regeneration 1 promote alveolar fluid clearance by activating alveolar epithelial sodium channels and Na, K-ATPase in lipopolysaccharide-induced acute lung injury. J Pharmacol Exp Ther. 379:156–165. 2021. View Article : Google Scholar : PubMed/NCBI

101 

Wang C, Meng Y, Wang Y, Jiang Z, Xu M, Bo L and Deng X: Ouabain protects mice against lipopolysaccharide-induced acute lung injury. Med Sci Monit. 24:4455–4464. 2018. View Article : Google Scholar : PubMed/NCBI

102 

Wang Q, Lian QQ, Li R, Ying BY, He Q, Chen F, Zheng X, Yang Y, Wu DR, Zheng SX, et al: Lipoxin A(4) activates alveolar epithelial sodium channel, Na,K-ATPase, and increases alveolar fluid clearance. Am J Respir Cell Mol Biol. 48:610–618. 2013. View Article : Google Scholar : PubMed/NCBI

103 

Emr BM, Roy S, Kollisch-Singule M, Gatto LA, Barravecchia M, Lin X, Young JL, Wang G, Liu J, Satalin J, et al: Electroporation-mediated gene delivery of Na+,K+-ATPase, and ENaC subunits to the lung attenuates acute respiratory distress syndrome in a two-hit porcine model. Shock. 43:16–23. 2015. View Article : Google Scholar : PubMed/NCBI

104 

Stern M, Ulrich K, Robinson C, Copeland J, Griesenbach U, Masse C, Cheng S, Munkonge F, Geddes D, Berthiaume Y and Alton E: Pretreatment with cationic lipid-mediated transfer of the Na+K+-ATPase pump in a mouse model in vivo augments resolution of high permeability pulmonary edema. Gene Ther. 7:960–966. 2000. View Article : Google Scholar : PubMed/NCBI

105 

Zhang J, Chang J, Beg MA, Huang W, Zhao Y, Dai W, Wu X, Cui W, Pillai SS, Lakhani HV, et al: Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn. iScience. 25:1049632022. View Article : Google Scholar : PubMed/NCBI

106 

Flodby P, Kim YH, Beard LL, Gao D, Ji Y, Kage H, Liebler JM, Minoo P, Kim KJ, Borok Z and Crandall ED: Knockout mice reveal a major role for alveolar epithelial type I cells in alveolar fluid clearance. Am J Respir Cell Mol Biol. 55:395–406. 2016. View Article : Google Scholar : PubMed/NCBI

107 

Li G, Flodby P, Luo J, Kage H, Sipos A, Gao D, Ji Y, Beard LL, Marconett CN, DeMaio L, et al: Knockout mice reveal key roles for claudin 18 in alveolar barrier properties and fluid homeostasis. Am J Respir Cell Mol Biol. 51:210–222. 2014. View Article : Google Scholar : PubMed/NCBI

108 

Lin X, Barravecchia M, Kothari P, Young JL and Dean DA: β1-Na(+),K(+)-ATPase gene therapy upregulates tight junctions to rescue lipopolysaccharide-induced acute lung injury. Gene Ther. 23:489–499. 2016. View Article : Google Scholar : PubMed/NCBI

109 

Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, Buchwald M and Tsui LC: Identification of the cystic fibrosis gene: Genetic analysis. Science. 245:1073–1080. 1989. View Article : Google Scholar : PubMed/NCBI

110 

Riordan JR, Romments JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, et al: Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science. 245:1066–1073. 1989. View Article : Google Scholar : PubMed/NCBI

111 

Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, et al: Identification of the cystic fibrosis gene: Chromosome walking and jumping. Science. 245:1059–1065. 1989. View Article : Google Scholar : PubMed/NCBI

112 

Endres TM and Konstan MW: What is cystic fibrosis? JAMA. 327:1912022. View Article : Google Scholar : PubMed/NCBI

113 

Rafeeq MM and Murad HAS: Cystic fibrosis: Current therapeutic targets and future approaches. J Transl Med. 15:842017. View Article : Google Scholar : PubMed/NCBI

114 

Natarajan V: Is PI3K a villain in cystic fibrosis? Am J Respir Cell Mol Biol. 62:552–553. 2020. View Article : Google Scholar : PubMed/NCBI

115 

Reilly R, Mroz MS, Dempsey E, Wynne K, Keely SJ, McKone EF, Hiebel C, Behl C and Coppinger JA: Targeting the PI3K/Akt/mTOR signalling pathway in cystic fibrosis. Sci Rep. 7:76422017. View Article : Google Scholar : PubMed/NCBI

116 

Peckham D, Holland E, Range S and Knox AJ: Na+/K+ ATPase in lower airway epithelium from cystic fibrosis and non-cystic-fibrosis lung. Biochem Biophys Res Commun. 232:464–468. 1997. View Article : Google Scholar : PubMed/NCBI

117 

Luczay A, Vásárhelyi B, Dobos M, Holics K, Ujhelyi R and Tulassay T: Altered erythrocyte sodium-lithium counter-transport and Na+/K(+)-ATPase activity in cystic fibrosis. Acta Paediatr. 86:245–247. 1997. View Article : Google Scholar : PubMed/NCBI

118 

Miller TJ and Davis PB: FXYD5 modulates Na+ absorption and is increased in cystic fibrosis airway epithelia. Am J Physiol Lung Cell Mol Physiol. 294:L654–L664. 2008. View Article : Google Scholar : PubMed/NCBI

119 

Raghavan D, Gao A, Ahn C, Kaza V, Finklea J, Torres F and Jain R: Lung transplantation and gender effects on survival of recipients with cystic fibrosis. J Heart Lung Transplant. 35:1487–1496. 2016. View Article : Google Scholar : PubMed/NCBI

120 

Saint-Criq V, Kim SH, Katzenellenbogen JA and Harvey BJ: Non-genomic estrogen regulation of ion transport and airway surface liquid dynamics in cystic fibrosis bronchial epithelium. PLoS One. 8:e785932013. View Article : Google Scholar : PubMed/NCBI

121 

Matalon S, Bartoszewski R and Collawn JF: Role of epithelial sodium channels in the regulation of lung fluid homeostasis. Am J Physiol Lung Cell Mol Physiol. 309:L1229–L1238. 2015. View Article : Google Scholar : PubMed/NCBI

122 

Richeldi L, Collard HR and Jones MG: Idiopathic pulmonary fibrosis. Lancet. 389:1941–1952. 2017. View Article : Google Scholar : PubMed/NCBI

123 

Cai M, Zhu M, Ban C, Su J, Ye Q, Liu Y, Zhao W, Wang C and Dai H: Clinical features and outcomes of 210 patients with idiopathic pulmonary fibrosis. Chin Med J (Engl). 127:1868–1873. 2014. View Article : Google Scholar : PubMed/NCBI

124 

Li B, Huang X, Xu X, Ning W, Dai H and Wang C: The profibrotic effect of downregulated Na,K-ATPase β1 subunit in alveolar epithelial cells during lung fibrosis. Int J Mol Med. 44:273–280. 2019.PubMed/NCBI

125 

Rodrigo R, Trujillo S, Bosco C, Orellana M, Thielemann L and Araya J: Changes in (Na + K)-adenosine triphosphatase activity and ultrastructure of lung and kidney associated with oxidative stress induced by acute ethanol intoxication. Chest. 121:589–596. 2002. View Article : Google Scholar : PubMed/NCBI

126 

Nam LB and Keum YS: Regulation of NRF2 by Na+/K+-ATPase: Implication of tyrosine phosphorylation of Src. Free Radic Res. 54:883–893. 2020. View Article : Google Scholar : PubMed/NCBI

127 

Wang J, Hu K, Cai X, Yang B, He Q, Wang J and Weng Q: Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis. Acta Pharm Sin B. 12:18–32. 2022. View Article : Google Scholar : PubMed/NCBI

128 

Ludens JH, Clark MA, DuCharme DW, Harris DW, Lutzke BS, Mandel F, Mathews WR, Sutter DM and Hamlyn JM: Purification of an endogenous digitalislike factor from human plasma for structural analysis. Hypertension. 17:923–929. 1991. View Article : Google Scholar : PubMed/NCBI

129 

Sophocleous A, Elmatzoglou I and Souvatzoglou A: Circulating endogenous digitalis-like factor(s) (EDLF) in man is derived from the adrenals and its secretion is ACTH-dependent. J Endocrinol Invest. 26:668–674. 2003. View Article : Google Scholar : PubMed/NCBI

130 

Li B, Huang X, Liu Z, Xu X, Xiao H, Zhang X, Dai H and Wang C: Ouabain ameliorates bleomycin induced pulmonary fibrosis by inhibiting proliferation and promoting apoptosis of lung fibroblasts. Am J Transl Res. 10:2967–2974. 2018.PubMed/NCBI

131 

La J, Reed EB, Koltsova S, Akimova O, Hamanaka RB, Mutlu GM, Orlov SN and Dulin NO: Regulation of myofibroblast differentiation by cardiac glycosides. Am J Physiol Lung Cell Mol Physiol. 310:L815–L823. 2016. View Article : Google Scholar : PubMed/NCBI

132 

Orlov SN, La J, Smolyaninova LV and Dulin NO: Na+,K+-ATPase as a target for treatment of tissue fibrosis. Curr Med Chem. 26:564–575. 2019. View Article : Google Scholar : PubMed/NCBI

133 

Johnson S, Sommer N, Cox-Flaherty K, Weissmann N, Ventetuolo CE and Maron BA: Pulmonary hypertension: A contemporary review. Am J Respir Crit Care Med. 208:528–548. 2023. View Article : Google Scholar : PubMed/NCBI

134 

Mocumbi A, Humbert M, Saxena A, Jing ZC, Sliwa K, Thienemann F, Archer SL and Stewart S: Pulmonary hypertension. Nat Rev Dis Primers. 10:12024. View Article : Google Scholar : PubMed/NCBI

135 

Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, et al: 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 61:22008792023. View Article : Google Scholar : PubMed/NCBI

136 

Kovacs G, Bartolome S, Denton CP, Gatzoulis MA, Gu S, Khanna D, Badesch D and Montani D: Definition, classification and diagnosis of pulmonary hypertension. Eur Respir J. 64:24013242024. View Article : Google Scholar : PubMed/NCBI

137 

Poch D and Mandel J: Pulmonary hypertension. Ann Intern Med. 174:ITC49–ITC64. 2021. View Article : Google Scholar : PubMed/NCBI

138 

Bubb KJ, Tang O, Gentile C, Moosavi SM, Hansen T, Liu CC, Di Bartolo BA and Figtree GA: FXYD1 is protective against vascular dysfunction. Hypertension. 77:2104–2116. 2021. View Article : Google Scholar : PubMed/NCBI

139 

Pavlovic D, Hall AR, Kennington EJ, Aughton K, Boguslavskyi A, Fuller W, Despa S, Bers DM and Shattock MJ: Nitric oxide regulates cardiac intracellular Na+ and Ca2+by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism. J Mol Cell Cardiol. 61:164–171. 2013. View Article : Google Scholar : PubMed/NCBI

140 

Hansen TS, Karimi Galougahi K, Tang O, Tsang M, Scherrer-Crosbie M, Arystarkhova E, Sweadner K, Bursill C, Bubb KJ and Figtree GA: The FXYD1 protein plays a protective role against pulmonary hypertension and arterial remodeling via redox and inflammatory mechanisms. Am J Physiol Heart Circ Physiol. 326:H623–H635. 2024. View Article : Google Scholar : PubMed/NCBI

141 

Ghosh B, Kar P, Mandal A, Dey K, Chakraborti T and Chakraborti S: Ca2+ influx mechanisms in caveolae vesicles of pulmonary smooth muscle plasma membrane under inhibition of alpha2beta1 isozyme of Na+/K+-ATPase by ouabain. Life Sci. 84:139–148. 2009. View Article : Google Scholar : PubMed/NCBI

142 

Fürstenwerth H: Ouabain-the insulin of the heart. Int J Clin Pract. 64:1591–1594. 2010. View Article : Google Scholar : PubMed/NCBI

143 

Guerrero A, Herranz N, Sun B, Wagner V, Gallage S, Guiho R, Wolter K, Pombo J, Irvine EE, Innes AJ, et al: Cardiac glycosides are broad-spectrum senolytics. Nat Metab. 1:1074–1088. 2019. View Article : Google Scholar : PubMed/NCBI

144 

Laredo J, Hamilton BP and Hamlyn JM: Secretion of endogenous ouabain from bovine adrenocortical cells: Role of the zona glomerulosa and zona fasciculata. Biochem Biophys Res Commun. 212:487–493. 1995. View Article : Google Scholar : PubMed/NCBI

145 

De Angelis C and Haupert GT Jr: Hypoxia triggers release of an endogenous inhibitor of Na(+)-K(+)-ATPase from midbrain and adrenal. Am J Physiol. 274:F182–F188. 1998.PubMed/NCBI

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Spandidos Publications style
Liu Z, Dong T, Li F, He C, Zhang W and Li B: The role of Na,K‑ATPase in lung diseases (Review). Mol Med Rep 32: 300, 2025.
APA
Liu, Z., Dong, T., Li, F., He, C., Zhang, W., & Li, B. (2025). The role of Na,K‑ATPase in lung diseases (Review). Molecular Medicine Reports, 32, 300. https://doi.org/10.3892/mmr.2025.13665
MLA
Liu, Z., Dong, T., Li, F., He, C., Zhang, W., Li, B."The role of Na,K‑ATPase in lung diseases (Review)". Molecular Medicine Reports 32.5 (2025): 300.
Chicago
Liu, Z., Dong, T., Li, F., He, C., Zhang, W., Li, B."The role of Na,K‑ATPase in lung diseases (Review)". Molecular Medicine Reports 32, no. 5 (2025): 300. https://doi.org/10.3892/mmr.2025.13665
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Z, Dong T, Li F, He C, Zhang W and Li B: The role of Na,K‑ATPase in lung diseases (Review). Mol Med Rep 32: 300, 2025.
APA
Liu, Z., Dong, T., Li, F., He, C., Zhang, W., & Li, B. (2025). The role of Na,K‑ATPase in lung diseases (Review). Molecular Medicine Reports, 32, 300. https://doi.org/10.3892/mmr.2025.13665
MLA
Liu, Z., Dong, T., Li, F., He, C., Zhang, W., Li, B."The role of Na,K‑ATPase in lung diseases (Review)". Molecular Medicine Reports 32.5 (2025): 300.
Chicago
Liu, Z., Dong, T., Li, F., He, C., Zhang, W., Li, B."The role of Na,K‑ATPase in lung diseases (Review)". Molecular Medicine Reports 32, no. 5 (2025): 300. https://doi.org/10.3892/mmr.2025.13665
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