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

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...

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Autores principales: McNair, Andrew J., Wilson, Kathryn S., Martin, Patricia E., Welsh, David J., Dempsie, Yvonne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338651/
https://www.ncbi.nlm.nih.gov/pubmed/32670564
http://dx.doi.org/10.1177/2045894020937134
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author McNair, Andrew J.
Wilson, Kathryn S.
Martin, Patricia E.
Welsh, David J.
Dempsie, Yvonne
author_facet McNair, Andrew J.
Wilson, Kathryn S.
Martin, Patricia E.
Welsh, David J.
Dempsie, Yvonne
author_sort McNair, Andrew J.
collection PubMed
description 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 phosphorylation in rPAFs were attenuated in the presence of Gap27 or Cx43 siRNA. Cx43 protein expression was increased in sugen5416/hypoxic rat lung; this increased expression was not observed in sugen5416/hypoxic rats treated with the MAPK pathway inhibitor GS-444217. In conclusion, Cx43 is involved in the proliferation and migration of rPAFs in response to hypoxia via the MAPK signalling pathway.
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spelling pubmed-73386512020-07-14 Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia McNair, Andrew J. Wilson, Kathryn S. Martin, Patricia E. Welsh, David J. Dempsie, Yvonne Pulm Circ Research Article 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 phosphorylation in rPAFs were attenuated in the presence of Gap27 or Cx43 siRNA. Cx43 protein expression was increased in sugen5416/hypoxic rat lung; this increased expression was not observed in sugen5416/hypoxic rats treated with the MAPK pathway inhibitor GS-444217. In conclusion, Cx43 is involved in the proliferation and migration of rPAFs in response to hypoxia via the MAPK signalling pathway. SAGE Publications 2020-07-06 /pmc/articles/PMC7338651/ /pubmed/32670564 http://dx.doi.org/10.1177/2045894020937134 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/ Creative Commons CC-BY: This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
McNair, Andrew J.
Wilson, Kathryn S.
Martin, Patricia E.
Welsh, David J.
Dempsie, Yvonne
Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia
title Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia
title_full Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia
title_fullStr Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia
title_full_unstemmed Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia
title_short Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia
title_sort connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338651/
https://www.ncbi.nlm.nih.gov/pubmed/32670564
http://dx.doi.org/10.1177/2045894020937134
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