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Article

Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling

  • Authors:
    • Jingchang Zhang
    • Qiming Liu
    • Zhenfei Fang
    • Xinqun Hu
    • Feng Huang
    • Liang Tang
    • Shenghua Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530000, P.R. China, Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, P.R. China, Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530000, P.R. China
  • Pages: 1801-1806
    |
    Published online on: December 17, 2015
       https://doi.org/10.3892/mmr.2015.4691
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Abstract

Endothelial progenitor cells (EPCs) can form new vessels through differentiation into endothelial cells (ECs), thus being important in the prevention of hypoxia/ischemia. Apelin can activate different signaling pathways through its receptor, APLNR, which regulate diverse biological functions, including cardiovascular function. However, the molecular mechanism by which Apelin mediates hypoxia‑induced EPCs proliferation remain to be fully elucidated. The present study aimed to determine the role of Apelin/APLNR signaling in hypoxia‑induced proliferation of EPCs. MTT assay was used to determine cell proliferation. Reverse transcription-quantitative polymerase chain reaction and western blotting analysis were conducted to examine mRNA and protein expression. It was revealed that hypoxia promoted the proliferation of the EPCs. Further investigation demonstrated that hypoxia promoted the expression levels of hypoxia‑inducible factor (HIF)‑1α, Apelin and APLNR in the EPCs. In addition, upregulation of Apelin or APLNR promoted the hypoxia‑induced proliferation of the EPCs, while knockdown of Apelin or APLNR by small interfering RNA suppressed the hypoxia‑induced proliferation of the EPCs, suggesting that the Apelin/APLNR axis is involved in hypoxia‑induced proliferation of EPCs. Furthermore, pretreatment of the EPCs with SB‑239063 or PD98059, two inhibitors of mitogen‑activated protein kinase (MAPK), eliminated the Apelin upregulation‑induced EPC proliferation, suggesting that MAPK signaling is a downstream effecter of Apelin/APLNR in EPCs. Therefore, the findings of the present study indicated that the production of HIF‑1α, induced by hypoxia, activated the Apelin/APLNR and the downstream MAPK signaling pathways, leading to upregulated proliferation of the EPCs. These findings suggested that Apelin/APLNR signaling may be used as a potential therapeutic target for hypoxic/ischemic injury.
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View References

1 

Endemann DH and Schiffrin EL: Endothelial dysfunction. J Am Soc Nephrol. 15:1983–1992. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Schröder K, Kohnen A, Aicher A, Liehn EA, Büchse T, Stein S, Weber C, Dimmeler S and Brandes RP: NADPH oxidase Nox2 is required for hypoxia-induced mobilization of endothelial progenitor cells. Circ Res. 105:537–544. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Simons D, Grieb G, Hristov M, Pallua N, Weber C, Bernhagen J and Steffens G: Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor and role in endothelial progenitor cell recruitment. J Cell Mol Med. 15:668–678. 2011. View Article : Google Scholar

4 

Jiang M, Wang CQ, Wang BY and Huang DJ: Inhibitory effect of siRNA targeting HIF-1alpha on differentiation of peripheral blood endothelial progenitor cells. Ai Zheng. 24:1293–1300. 2005.In Chinese.

5 

Kleinz MJ and Baxter GF: Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase. Regul Pept. 146:271–277. 2008. View Article : Google Scholar

6 

Zhang Z, Yu B and Tao GZ: Apelin protects against cardiomyocyte apoptosis induced by glucose deprivation. Chin Med J (Engl). 122:2360–2365. 2009.

7 

Ye J, Ni P, Kang L and Xu B: Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction. J Biomed Res. 26:400–409. 2012. View Article : Google Scholar

8 

Wang W, McKinnie SM, Patel VB, Haddad G, Wang Z, Zhabyeyev P, Das SK, Basu R, McLean B, Kandalam V, et al: Loss of Apelin exacerbates myocardial infarction adverse remodeling and ischemia-reperfusion injury: Therapeutic potential of synthetic Apelin analogues. J Am Heart Assoc. 2:e0002492013. View Article : Google Scholar : PubMed/NCBI

9 

Kyriakis JM and Avruch J: Mammalian MAPK signal transduction pathways activated by stress and inflammation: A 10-year update. Physiol Rev. 92:689–737. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Qiu C, Xie Q, Zhang D, Chen Q, Hu J and Xu L: GM-CSF induces cyclin D1 expression and proliferation of endothelial progenitor cells via PI3K and MAPK signaling. Cell Physiol Biochem. 33:784–795. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Zhang J, Liu Q, Hu X, Fang Z, Huang F, Tang L and Zhou S: Apelin/APJ signaling promotes hypoxia-induced proliferation of endothelial progenitor cells via phosphoinositide-3 kinase/Akt signaling. Mol Med Rep. 12:3829–3834. 2015.PubMed/NCBI

12 

Zhong Y, Lin Y, Shen S, Zhou Y, Mao F, Guan J and Sun Q: Expression of ALDH1 in breast invasive ductal carcinoma: An independent predictor of early tumor relapse. Cancer Cell Int. 13:602013. View Article : Google Scholar : PubMed/NCBI

13 

O'Carroll AM, Lolait SJ, Harris LE and Pope GR: The Apelin receptor APJ: Journey from an orphan to a multifaceted regulator of homeostasis. J Endocrinol. 219:R13–R35. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Dai T, Zheng H and Fu GS: Hypoxia confers protection against apoptosis via the PI3K/Akt pathway in endothelial progenitor cells. Acta Pharmacol Sin. 29:1425–1431. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Lee SH, Lee JH, Yoo SY, Hur J, Kim HS and Kwon SM: Hypoxia inhibits cellular senescence to restore the therapeutic potential of old human endothelial progenitor cells via the hypoxia-inducible factor-1alpha-TWIST-p21 axis. Arterioscler Thromb Vasc Biol. 33:2407–2414. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Machalińska A: The role of circulating endothelial progenitor cells in the development of vascular retinal diseases. Klin Oczna. 115:158–162. 2013.In Polish.

17 

Jiang M, Wang B, Wang C, He B, Fan H, Guo TB, Shao Q, Gao L and Liu Y: Inhibition of hypoxia-inducible factor-1alpha and endothelial progenitor cell differentiation by adenoviral transfer of small interfering RNA in vitro. J Vasc Res. 43:511–521. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Jiang M, Wang CQ, Wang BY, He B, Shao Q and Huang DJ: Overexpression of hypoxia inducible factor-1alpha (HIF-1alpha) promotes the differentiation of endothelial progenitor cell ex vivo. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 14:565–570. 2006.In Chinese. PubMed/NCBI

19 

Li L, Zeng H and Chen JX: Apelin-13 increases myocardial progenitor cells and improves repair postmyocardial infarction. Am J Physiol Heart Circ Physiol. 303:H605–H618. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Lv D, Li H and Chen L: Apelin and APJ, a novel critical factor and therapeutic target for atherosclerosis. Acta Biochim Biophys Sin (Shanghai). 45:527–533. 2013. View Article : Google Scholar

21 

Kasai A, Ishimaru Y, Higashino K, Kobayashi K, Yamamuro A, Yoshioka Y and Maeda S: Inhibition of Apelin expression switches endothelial cells from proliferative to mature state in pathological retinal angiogenesis. Angiogenesis. 16:723–734. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Glassford AJ, Yue P, Sheikh AY, Chun HJ, Zarafshar S, Chan DA, Reaven GM, Quertermous T and Tsao PS: HIF-1 regulates hypoxia- and insulin-induced expression of Apelin in adipocytes. Am J Physiol Endocrinol Metab. 293:E1590–E1596. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Ronkainen VP, Ronkainen JJ, Hänninen SL, Leskinen H, Ruas JL, Pereira T, Poellinger L, Vuolteenaho O and Tavi P: Hypoxia inducible factor regulates the cardiac expression and secretion of Apelin. FASEB J. 21:1821–1830. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Than A, Zhang X, Leow MK, Poh CL, Chong SK and Chen P: Apelin attenuates oxidative stress in human adipocytes. J Biol Chem. 289:3763–3774. 2014. View Article : Google Scholar :

25 

Yang Y, Zhang X, Cui H, Zhang C, Zhu C and Li L: Apelin-13 protects the brain against ischemia/reperfusion injury through activating PI3K/Akt and ERK1/2 signaling pathways. Neurosci Lett. 568:44–49. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang J, Liu Q, Fang Z, Hu X, Huang F, Tang L and Zhou S: Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling. Mol Med Rep 13: 1801-1806, 2016.
APA
Zhang, J., Liu, Q., Fang, Z., Hu, X., Huang, F., Tang, L., & Zhou, S. (2016). Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling. Molecular Medicine Reports, 13, 1801-1806. https://doi.org/10.3892/mmr.2015.4691
MLA
Zhang, J., Liu, Q., Fang, Z., Hu, X., Huang, F., Tang, L., Zhou, S."Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling". Molecular Medicine Reports 13.2 (2016): 1801-1806.
Chicago
Zhang, J., Liu, Q., Fang, Z., Hu, X., Huang, F., Tang, L., Zhou, S."Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling". Molecular Medicine Reports 13, no. 2 (2016): 1801-1806. https://doi.org/10.3892/mmr.2015.4691
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang J, Liu Q, Fang Z, Hu X, Huang F, Tang L and Zhou S: Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling. Mol Med Rep 13: 1801-1806, 2016.
APA
Zhang, J., Liu, Q., Fang, Z., Hu, X., Huang, F., Tang, L., & Zhou, S. (2016). Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling. Molecular Medicine Reports, 13, 1801-1806. https://doi.org/10.3892/mmr.2015.4691
MLA
Zhang, J., Liu, Q., Fang, Z., Hu, X., Huang, F., Tang, L., Zhou, S."Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling". Molecular Medicine Reports 13.2 (2016): 1801-1806.
Chicago
Zhang, J., Liu, Q., Fang, Z., Hu, X., Huang, F., Tang, L., Zhou, S."Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling". Molecular Medicine Reports 13, no. 2 (2016): 1801-1806. https://doi.org/10.3892/mmr.2015.4691
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