HIF-1α promotes the proliferation and migration of pulmonary arterial smooth muscle cells via activation of Cx43.

Content Provider	Europe PMC
Author	Han, Xiao‐Jian Zhang, Wei‐Fang Wang, Qin Li, Min Zhang, Chun‐Bo Yang, Zhang‐Jian Tan, Ren‐Jie Gan, Li‐Jun Zhang, Le‐Ling Lan, Xue‐Mei Zhang, Fang‐Lin Hong, Tao Jiang, Li‐Ping
Abstract	AbstractThe proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important cause of pulmonary vascular remodelling in hypoxia‐induced pulmonary hypertension (HPH). However, its underlying mechanism has not been well elucidated. Connexin 43 (Cx43) plays crucial roles in vascular smooth muscle cell proliferation in various cardiovascular diseases. Here, the male Sprague‐Dawley (SD) rats were exposed to hypoxia (10% O2) for 21 days to induce rat HPH model. PASMCs were treated with CoCl2 (200 µM) for 24 h to establish the HPH cell model. It was found that hypoxia up‐regulated the expression of Cx43 and phosphorylation of Cx43 at Ser 368 in rat pulmonary arteries and PASMCs, and stimulated the proliferation and migration of PASMCs. HIF‐1α inhibitor echinomycin attenuated the CoCl2‐induced Cx43 expression and phosphorylation of Cx43 at Ser 368 in PASMCs. The interaction between HIF‐1α and Cx43 promotor was also identified using chromatin immunoprecipitation assay. Moreover, Cx43 specific blocker (37,43Gap27) or knockdown of Cx43 efficiently alleviated the proliferation and migration of PASMCs under chemically induced hypoxia. Therefore, the results above suggest that HIF‐1α, as an upstream regulator, promotes the expression of Cx43, and the HIF‐1α/Cx43 axis regulates the proliferation and migration of PASMCs in HPH.
Page Count	11
ISSN	15821838
Journal	Journal of Cellular and Molecular Medicine
Volume Number	25
PubMed Central reference number	PMC8581339
Issue Number	22
PubMed reference number	34698450
e-ISSN	15824934
DOI	10.1111/jcmm.17003
Language	English
Publisher	John Wiley and Sons Inc.
Publisher Date	2021-10-26
Publisher Place	Hoboken
Access Restriction	Open
Rights License	This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Subject Keyword	connexin 43 hypoxia hypoxia‐induced pulmonary hypertension migration proliferation pulmonary artery smooth muscle cells
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Medicine