Recombinant high‑mobility group box 1 induces cardiomyocyte hypertrophy by regulating the 14‑3‑3η, PI3K and nuclear factor of activated T cells signaling pathways

Su,Feifei; Shi,Miaoqian; Zhang,Jian; Li,Yan; Tian,Jianwei

doi:10.3892/mmr.2021.11853

Recombinant high‑mobility group box 1 induces cardiomyocyte hypertrophy by regulating the 14‑3‑3η, PI3K and nuclear factor of activated T cells signaling pathways

Authors:
- Feifei Su
- Miaoqian Shi
- Jian Zhang
- Yan Li
- Jianwei Tian
View Affiliations

Affiliations: Department of Cardiology, Air Force Medical Center, People's Liberation Army, Beijing 100142, P.R. China, Department of Cardiology, The Seventh Medical Centre of The People's Liberation Army General Hospital, Beijing 100700, P.R. China, Department of Cardiology, Beijing Chest Hospital Heart Center, Capital Medical University, Beijing 101149, P.R. China, Department of Cardiology, Tangdu Hospital Affiliated to The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
Published online on: January 20, 2021 https://doi.org/10.3892/mmr.2021.11853
Article Number: 214
Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

High‑mobility group box 1 (HMGB1) is released by necrotic cells and serves an important role in cardiovascular pathology. However, the effects of HMGB1 in cardiomyocyte hypertrophy remain unclear. Therefore, the aim of the present study was to investigate the potential role of HMGB1 in cardiomyocyte hypertrophy and the underlying mechanisms of its action. Neonatal mouse cardiomyocytes (NMCs) were co‑cultured with recombinant HMGB1 (rHMGB1). Wortmannin was used to inhibit PI3K activity in cardiomyocytes. Subsequently, atrial natriuretic peptide (ANP), 14‑3‑3 and phosphorylated‑Akt (p‑Akt) protein levels were detected using western blot analysis. In addition, nuclear factor of activated T cells 3 (NFAT3) protein levels were measured by western blot analysis and observed in NMCs under a confocal microscope. The results revealed that rHMGB1 increased ANP and p‑Akt, and decreased 14‑3‑3η protein levels. Furthermore, wortmannin abrogated the effects of rHMGB1 on ANP, 14‑3‑3η and p‑Akt protein levels. In addition, rHMGB1 induced nuclear translocation of NFAT3, which was also inhibited by wortmannin pretreatment. The results of this study suggest that rHMGB1 induces cardiac hypertrophy by regulating the 14‑3‑3η/PI3K/Akt/NFAT3 signaling pathway.

View Figures

View References

1	Biscetti F, Flex A, Alivernini S, Tolusso B, Gremese E and Ferraccioli G: The role of high-mobility group Box-1 and its crosstalk with microbiome in rheumatoid arthritis. Mediators Inflamm. 2017:52303742017. View Article : Google Scholar : PubMed/NCBI
2	Bangert A, Andrassy M, Muller AM, Bockstahler M, Fischer A, Volz CH, Leib C, Göser S, Korkmaz-Icöz S, Zittrich S, et al: Critical role of RAGE and HMGB1 in inflammatory heart disease. Proc Natl Acad Sci USA. 113:E155–E164. 2016. View Article : Google Scholar : PubMed/NCBI
3	Dong LY, Chen F, Xu M, Yao LP, Zhang YJ and Zhuang Y: Quercetin attenuates myocardial ischemia-reperfusion injury via downregulation of the HMGB1-TLR4-NF-kB signaling pathway. Am J Transl Res. 10:1273–1283. 2018.PubMed/NCBI
4	Zhang W, Tao A, Lan T, Cepinskas G, Kao R, Martin CM and Rui T: Carbon monoxide releasing molecule-3 improves myocardial function in mice with sepsis by inhibiting NLRP3 inflammasome activation in cardiac fibroblasts. Basic Res Cardiol. 112:162017. View Article : Google Scholar : PubMed/NCBI
5	Wu RN, Yu TY, Zhou JC, Li M, Gao HK, Zhao C, Dong RQ, Peng D, Hu ZW, Zhang XW and Wu YQ: Targeting HMGB1 ameliorates cardiac fibrosis through restoring TLR2-mediated autophagy suppression in myocardial fibroblasts. Int J Cardiol. 267:156–162. 2018. View Article : Google Scholar : PubMed/NCBI
6	Shen W, Zhou J, Wang C, Xu G, Wu Y and Hu Z: High mobility group box 1 induces calcification of aortic valve interstitial cells via toll-like receptor 4. Mol Med Rep. 15:2530–2536. 2017. View Article : Google Scholar : PubMed/NCBI
7	Lv Q, Li C, Mo Y and He L: The role of HMGB1 in heart transplantation. Immunol Lett. 194:1–3. 2018. View Article : Google Scholar : PubMed/NCBI
8	Su FF, Shi MQ, Guo WG, Liu XT, Wang HT, Lu ZF and Zheng QS: High-mobility group box 1 induces calcineurin-mediated cell hypertrophy in neonatal rat ventricular myocytes. Mediators Inflamm. 2012:8051492012. View Article : Google Scholar : PubMed/NCBI
9	Nehra S, Bhardwaj V, Kalra N, Ganju L, Bansal A, Saxena S and Saraswat D: Nanocurcumin protects cardiomyoblasts H9c2 from hypoxia-induced hypertrophy and apoptosis by improving oxidative balance. J Physiol Biochem. 71:239–251. 2015. View Article : Google Scholar : PubMed/NCBI
10	Fang X, Liu Y, Lu J, Hong H, Yuan J, Zhang Y, Wang P, Liu P and Ye J: Protocatechuic aldehyde protects against isoproterenol-induced cardiac hypertrophy via inhibition of the JAK2/STAT3 signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 391:1373–1385. 2018. View Article : Google Scholar : PubMed/NCBI
11	Wang S, Han HM, Pan ZW, Hang PZ, Sun LH, Jiang YN, Song HX, Du ZM and Liu Y: Choline inhibits angiotensin II-induced cardiac hypertrophy by intracellular calcium signal and p38 MAPK pathway. Naunyn Schmiedebergs Arch Pharmacol. 385:823–831. 2012. View Article : Google Scholar : PubMed/NCBI
12	Zwadlo C, Schmidtmann E, Szaroszyk M, Kattih B, Froese N, Hinz H, Schmitto JD, Widder J, Batkai S, Bähre H, et al: Antiandrogenic therapy with finasteride attenuates cardiac hypertrophy and left ventricular dysfunction. Circulation. 131:1071–1081. 2015. View Article : Google Scholar : PubMed/NCBI
13	Song L, Wang L, Li F, Yukht A, Qin M, Ruther H, Yang M, Chaux A, Shah PK and Sharifi BG: Bone marrow-derived tenascin-C attenuates cardiac hypertrophy by controlling inflammation. J Am Coll Cardiol. 70:1601–1615. 2017. View Article : Google Scholar : PubMed/NCBI
14	Gendy AM, Abdallah DM and El-Abhar HS: The potential curative effect of rebamipide in hepatic ischemia/reperfusion injury. Naunyn Schmiedebergs Arch Pharmacol. 390:691–700. 2017. View Article : Google Scholar : PubMed/NCBI
15	Raucci A, Di Maggio S, Scavello F, D'Ambrosio A, Bianchi ME and Capogrossi MC: The Janus face of HMGB1 in heart disease: A necessary update. Cell Mol Life Sci. 76:211–229. 2019. View Article : Google Scholar : PubMed/NCBI
16	Foglio E, Puddighinu G, Germani A, Russo MA and Limana F: HMGB1 inhibits apoptosis following MI and induces autophagy via mTORC1 inhibition. J Cell Physiol. 232:1135–1143. 2017. View Article : Google Scholar : PubMed/NCBI
17	Zhang L, Liu M, Jiang H, Yu Y, Yu P, Tong R, Wu J, Zhang S, Yao K, Zou Y and Ge J: Extracellular high-mobility group box 1 mediates pressure overload-induced cardiac hypertrophy and heart failure. J Cell Mol Med. 20:459–470. 2016. View Article : Google Scholar : PubMed/NCBI
18	Funayama A, Shishido T, Netsu S, Narumi T, Kadowaki S, Takahashi H, Miyamoto T, Watanabe T, Woo CH, Abe J, et al: Cardiac nuclear high mobility group box 1 prevents the development of cardiac hypertrophy and heart failure. Cardiovasc Res. 99:657–664. 2013. View Article : Google Scholar : PubMed/NCBI
19	Liao W, Wang S, Han C and Zhang Y: 14-3-3 proteins regulate glycogen synthase 3beta phosphorylation and inhibit cardiomyocyte hypertrophy. FEBS J. 272:1845–1854. 2005. View Article : Google Scholar : PubMed/NCBI
20	Jia H, Liang Z, Zhang X, Wang J, Xu W and Qian H: 14-3-3 proteins: An important regulator of autophagy in diseases. Am J Transl Res. 9:4738–4746. 2017.PubMed/NCBI
21	Obsilova V, Kopecka M, Kosek D, Kacirova M, Kylarova S, Rezabkova L and Obsil T: Mechanisms of the 14-3-3 protein function: Regulation of protein function through conformational modulation. Physiol Res. 63 (Suppl 1):S155–S164. 2014. View Article : Google Scholar : PubMed/NCBI
22	Sreedhar R, Arumugam S, Thandavarayan RA, Karuppagounder V, Koga Y, Nakamura T, Harima M and Watanabe K: Role of 14-3-3 η protein on cardiac fatty acid metabolism and macrophage polarization after high fat diet induced type 2 diabetes mellitus. Int J Biochem Cell Biol. 88:92–99. 2017. View Article : Google Scholar : PubMed/NCBI
23	Sreedhar R, Arumugam S, Thandavarayan RA, Giridharan VV, Karuppagounder V, Pitchaimani V, Afrin R, Miyashita S, Nomoto M, Harima M, et al: Myocardial 14-3-3 η protein protects against mitochondria mediated apoptosis. Cell Signal. 27:770–776. 2015. View Article : Google Scholar : PubMed/NCBI
24	Sreedhar R, Arumugam S, Thandavarayan RA, Giridharan VV, Karuppagounder V, Pitchaimani V, Afrin R, Harima M, Nakamura M, Suzuki K, et al: Depletion of cardiac 14-3-3 η protein adversely influences pathologic cardiac remodeling during myocardial infarction after coronary artery ligation in mice. Int J Cardiol. 202:146–153. 2016. View Article : Google Scholar : PubMed/NCBI
25	Chhabra S, Fischer P, Takeuchi K, Dubey A, Ziarek JJ, Boeszoermenyi A, Mathieu D, Bermel W, E Davey N, Wagner G and Arthanari H: (15)N detection harnesses the slow relaxation property of nitrogen: Delivering enhanced resolution for intrinsically disordered proteins. Proc Natl Acad Sci USA. 115:E1710–E1719. 2018. View Article : Google Scholar : PubMed/NCBI
26	Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, et al: The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. 14:931–938. 2008. View Article : Google Scholar : PubMed/NCBI
27	Kumar S, Wang G, Liu W, Ding W, Dong M, Zheng N, Ye H and Liu J: Hypoxia-induced mitogenic factor promotes cardiac hypertrophy via calcium-dependent and hypoxia-inducible Factor-1α mechanisms. Hypertension. 72:331–342. 2018. View Article : Google Scholar : PubMed/NCBI
28	Grund A, Szaroszyk M, Doppner JK, Mohammadi MM, Kattih B, Korf-Klingebiel M, Gigina A, Scherr M, Kensah G, Jara-Avaca M, et al: A gene therapeutic approach to inhibit CIB1 ameliorates maladaptive remodeling in pressure overload. Cardiovasc Res. 115:71–82. 2019. View Article : Google Scholar : PubMed/NCBI
29	Gelinas R, Mailleux F, Dontaine J, Bultot L, Demeulder B, Ginion A, Daskalopoulos EP, Esfahani H, Dubois-Deruy E, Lauzier B, et al: AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation. Nat Commun. 9:3742018. View Article : Google Scholar : PubMed/NCBI
30	Su F, Shi M, Zhang J, Zheng Q, Zhang D, Zhang W, Wang H and Li X: Simvastatin protects heart from pressure overload injury by inhibiting excessive autophagy. Int J Med Sci. 15:1508–1516. 2018. View Article : Google Scholar : PubMed/NCBI
31	DeBosch B, Treskov I, Lupu TS, Weinheimer C, Kovacs A, Courtois M and Muslin AJ: Akt1 is required for physiological cardiac growth. Circulation. 113:2097–2104. 2006. View Article : Google Scholar : PubMed/NCBI
32	O'Neill BT, Kim J, Wende AR, Theobald HA, Tuinei J, Buchanan J, Guo A, Zaha VG, Davis DK, Schell JC, et al: A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochondrial adaptations that accompany physiological cardiac hypertrophy. Cell Metab. 6:294–306. 2007. View Article : Google Scholar : PubMed/NCBI
33	Gao RR, Wu XD, Jiang HM, Zhu YJ, Zhou YL, Zhang HF, Yao WM, Li YQ and Li XL: Traditional Chinese medicine Qiliqiangxin attenuates phenylephrine-induced cardiac hypertrophy via upregulating PPARγ and PGC-1α. Ann Transl Med. 6:1532018. View Article : Google Scholar : PubMed/NCBI
34	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
35	Lu F, Xing J, Zhang X, Dong S, Zhao Y, Wang L, Li H, Yang F, Xu C and Zhang W: Exogenous hydrogen sulfide prevents cardiomyocyte apoptosis from cardiac hypertrophy induced by isoproterenol. Mol Cell Biochem. 381:41–50. 2013. View Article : Google Scholar : PubMed/NCBI
36	Hwang JH, Chu H, Ahn Y, Kim J and Kim DY: HMGB1 promotes hair growth via the modulation of prostaglandin metabolism. Sci Rep. 9:66602019. View Article : Google Scholar : PubMed/NCBI
37	Muller S, Ronfani L and Bianchi ME: Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function. J Intern Med. 255:332–343. 2004. View Article : Google Scholar : PubMed/NCBI
38	Tang D, Shi Y, Kang R, Li T, Xiao W, Wang H and Xiao XZ: Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1. J Leukoc Biol. 81:741–747. 2007. View Article : Google Scholar : PubMed/NCBI
39	Xu H, Yao Y, Su Z, Yang Y, Kao R, Martin CM and Rui T: Endogenous HMGB1 contributes to ischemia-reperfusion-induced myocardial apoptosis by potentiating the effect of TNF-α/JNK. Am J Physiol Heart Circ Physiol. 300:H913–H921. 2011. View Article : Google Scholar : PubMed/NCBI
40	Watanabe K, Thandavarayan RA, Gurusamy N, Zhang S, Muslin AJ, Suzuki K, Tachikawa H, Kodama M and Aizawa Y: Role of 14-3-3 protein and oxidative stress in diabetic cardiomyopathy. Acta Physiol Hung. 96:277–287. 2009. View Article : Google Scholar : PubMed/NCBI
41	Thandavarayan RA, Watanabe K, Ma M, Veeraveedu PT, Gurusamy N, Palaniyandi SS, Zhang S, Muslin AJ, Kodama M and Aizawa Y: 14-3-3 protein regulates Ask1 signaling and protects against diabetic cardiomyopathy. Biochem Pharmacol. 75:1797–1806. 2008. View Article : Google Scholar : PubMed/NCBI
42	Lin H, Shen L, Zhang X, Xie J, Hao H, Zhang Y, Chen Z, Yamamoto H, Liao W, Bin J, et al: HMGB1-RAGE axis makes no contribution to cardiac remodeling induced by pressure-overload. PLoS One. 11:e1585142016.