Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia

Pulmonary Circulation
Andrew J McNairYvonne Dempsie

Abstract

Pulmonary hypertension (PH) is a disease associated with vasoconstriction and remodelling of the pulmonary vasculature. Pulmonary artery fibroblasts (PAFs) play an important role in hypoxic-induced remodelling. Connexin 43 (Cx43) is involved in cellular communication and regulation of the pulmonary vasculature. Using both in vitro and in vivo models of PH, the aims of this study were to (i) investigate the role of Cx43 in hypoxic-induced proliferation and migration of rat PAFs (rPAFs) and rat pulmonary artery smooth muscle cells (rPASMCs) and (ii) determine whether Cx43 expression is dysregulated in the rat sugen5416/hypoxic model of PH. The role of Cx43 in hypoxic-induced proliferation and migration was investigated using Gap27 (a pharmacological inhibitor of Cx43) or genetic knockdown of Cx43 using siRNA. Cx43 protein expression was increased by hypoxia in rPAFs but not rPASMCs. Hypoxic exposure, in the presence of serum, resulted in an increase in proliferation of rPAFs but not rPASMCs. Hypoxic exposure caused migration of rPAFs but not rPASMCs. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) and ERK1/2 were increased by hypoxia in rPAFs. The effects of hypoxia on proliferation, migration and MAPK phosphorylat...Continue Reading

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Citations

Jan 28, 2021·International Journal of Molecular Sciences·Kerstin BoenglerRainer Schulz
Jan 14, 2021·Transplantation Direct·Tara TalaieChristine L Lau
Oct 27, 2021·Journal of Cellular and Molecular Medicine·Xiao-Jian HanLi-Ping Jiang

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Methods Mentioned

BETA
electrophoresis
nucleic acid purification
PCR
transfection
co-immunoprecipitation

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