H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2

  • Authors:
    • Yunquan Li
    • Guohui Liu
    • Dianqi Cai
    • Baoying Pan
    • Yuese Lin
    • Xuandi Li
    • Shujuan Li
    • Ling Zhu
    • Xinxue Liao
    • Huishen Wang
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  • Published online on: December 9, 2013     https://doi.org/10.3892/ijmm.2013.1579
  • Pages: 359-366
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Abstract

The hypoxia-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main cause of pulmonary arterial hypertension (PAH), in which oxidative stress, cyclooxygenase (COX)-2 and hydrogen sulfide (H2S) all play an important role. In the present study, we aimed to examine the effects of H2S on the hypoxia-induced proliferation of human PASMCs (HPASMCs) and to elucidate the underlying mechanisms. The HPASMCs were treated with cobalt chloride (CoCl2), a hypoxia-mimicking agent, to establish a cellular model of hypoxic PAH. Prior to treatment with CoCl2, the cells were pre-conditioned with sodium hydrosulfide (NaHS), a donor of H2S. Cell proliferation, reactive oxygen species (ROS) production, COX-2 expression, prostacyclin (also known as prostaglandin I2 or PGI2) secretion and H2S levels were detected in the cells. The exposure of the HPASMCs to CoCl2 markedly increased cell proliferation, accompanied by a decrease in COX-2 expression, PGI2 secretion and H2S levels; however, the levels of ROS were not altered. Although the exogenous ROS donor, H2O2, triggered similar degrees of proliferation to CoCl2, the ROS scavenger, N-acetyl-L-cysteine (NAC), markedly abolished the H2O2‑induced cell proliferation, as opposed to the CoCl2-induced proliferation. The CoCl2-induced proliferation of HPASMCs was suppressed by exogenously applied PGI2. The addition of H2S (NaHS) attenuated the CoCl2-induced cell proliferation through the increase in the intercellular content of H2S. Importantly, the exposure of the cells to H2S suppressed the CoCl2-induced downregulation in COX-2 expression and PGI2 secretion from the HPASMCs. In conclusion, the results from the current study suggest that H2S enhances hypoxia-induced cell proliferation through the upregulation of COX-2/PGI2, as opposed to ROS.
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2014-February
Volume 33 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Li Y, Liu G, Cai D, Pan B, Lin Y, Li X, Li S, Zhu L, Liao X, Wang H, Wang H, et al: H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2. Int J Mol Med 33: 359-366, 2014
APA
Li, Y., Liu, G., Cai, D., Pan, B., Lin, Y., Li, X. ... Wang, H. (2014). H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2. International Journal of Molecular Medicine, 33, 359-366. https://doi.org/10.3892/ijmm.2013.1579
MLA
Li, Y., Liu, G., Cai, D., Pan, B., Lin, Y., Li, X., Li, S., Zhu, L., Liao, X., Wang, H."H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2". International Journal of Molecular Medicine 33.2 (2014): 359-366.
Chicago
Li, Y., Liu, G., Cai, D., Pan, B., Lin, Y., Li, X., Li, S., Zhu, L., Liao, X., Wang, H."H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2". International Journal of Molecular Medicine 33, no. 2 (2014): 359-366. https://doi.org/10.3892/ijmm.2013.1579