Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A

Abstract The vascular adventitia contains numerous cell types including fibroblasts, adipocytes, inflammatory cells, and progenitors embedded within a complex extracellular matrix (ECM) network. In response to vascular injury, adventitial progenitors and fibroblasts become activated and exhibit incr...

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Autores principales:	Dahai Wang, Nabil Rabhi, Shaw-Fang Yet, Stephen R. Farmer, Matthew D. Layne
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7add016385324b19ad6457c3a169e374
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spelling	oai:doaj.org-article:7add016385324b19ad6457c3a169e3742021-12-02T10:54:14ZAortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A10.1038/s41598-021-82941-72045-2322https://doaj.org/article/7add016385324b19ad6457c3a169e3742021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82941-7https://doaj.org/toc/2045-2322Abstract The vascular adventitia contains numerous cell types including fibroblasts, adipocytes, inflammatory cells, and progenitors embedded within a complex extracellular matrix (ECM) network. In response to vascular injury, adventitial progenitors and fibroblasts become activated and exhibit increased proliferative capacity and differentiate into contractile cells that remodel the ECM. These processes can lead to vascular fibrosis and disease progression. Our previous work established that the ECM protein aortic carboxypeptidase-like protein (ACLP) promotes fibrotic remodeling in the lung and is activated by vascular injury. It is currently unknown what controls vascular adventitial cell differentiation and if ACLP has a role in this process. Using purified mouse aortic adventitia Sca1+ progenitors, ACLP repressed stem cell markers (CD34, KLF4) and upregulated smooth muscle actin (SMA) and collagen I expression. ACLP enhanced myocardin-related transcription factor A (MRTFA) activity in adventitial cells by promoting MRTFA nuclear translocation. Sca1 cells from MRTFA-null mice exhibited reduced SMA and collagen expression induced by ACLP, indicating Sca1 cell differentiation is regulated in part by the ACLP-MRTFA axis. We determined that ACLP induced vessel contraction and increased adventitial collagen in an explant model. Collectively these studies identified ACLP as a mediator of adventitial cellular differentiation, which may result in pathological vessel remodeling.Dahai WangNabil RabhiShaw-Fang YetStephen R. FarmerMatthew D. LayneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dahai Wang Nabil Rabhi Shaw-Fang Yet Stephen R. Farmer Matthew D. Layne Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A
description	Abstract The vascular adventitia contains numerous cell types including fibroblasts, adipocytes, inflammatory cells, and progenitors embedded within a complex extracellular matrix (ECM) network. In response to vascular injury, adventitial progenitors and fibroblasts become activated and exhibit increased proliferative capacity and differentiate into contractile cells that remodel the ECM. These processes can lead to vascular fibrosis and disease progression. Our previous work established that the ECM protein aortic carboxypeptidase-like protein (ACLP) promotes fibrotic remodeling in the lung and is activated by vascular injury. It is currently unknown what controls vascular adventitial cell differentiation and if ACLP has a role in this process. Using purified mouse aortic adventitia Sca1+ progenitors, ACLP repressed stem cell markers (CD34, KLF4) and upregulated smooth muscle actin (SMA) and collagen I expression. ACLP enhanced myocardin-related transcription factor A (MRTFA) activity in adventitial cells by promoting MRTFA nuclear translocation. Sca1 cells from MRTFA-null mice exhibited reduced SMA and collagen expression induced by ACLP, indicating Sca1 cell differentiation is regulated in part by the ACLP-MRTFA axis. We determined that ACLP induced vessel contraction and increased adventitial collagen in an explant model. Collectively these studies identified ACLP as a mediator of adventitial cellular differentiation, which may result in pathological vessel remodeling.
format	article
author	Dahai Wang Nabil Rabhi Shaw-Fang Yet Stephen R. Farmer Matthew D. Layne
author_facet	Dahai Wang Nabil Rabhi Shaw-Fang Yet Stephen R. Farmer Matthew D. Layne
author_sort	Dahai Wang
title	Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A
title_short	Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A
title_full	Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A
title_fullStr	Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A
title_full_unstemmed	Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A
title_sort	aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor a
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7add016385324b19ad6457c3a169e374
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Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A

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