Cargando…

Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation

Smooth muscle cells (SMCs) in normal blood vessels exist in a highly differentiate state characterized by expression of SMC-specific contractile proteins (“contractile phenotype”). Following blood vessel injury in vivo or when cultured in vitro in the presence of multiple growth factors, SMC undergo...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Pei-Yu, Qin, Lingfeng, Li, Guangxin, Tellides, George, Simons, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025753/
https://www.ncbi.nlm.nih.gov/pubmed/27634335
http://dx.doi.org/10.1038/srep33407
_version_ 1782454011956297728
author Chen, Pei-Yu
Qin, Lingfeng
Li, Guangxin
Tellides, George
Simons, Michael
author_facet Chen, Pei-Yu
Qin, Lingfeng
Li, Guangxin
Tellides, George
Simons, Michael
author_sort Chen, Pei-Yu
collection PubMed
description Smooth muscle cells (SMCs) in normal blood vessels exist in a highly differentiate state characterized by expression of SMC-specific contractile proteins (“contractile phenotype”). Following blood vessel injury in vivo or when cultured in vitro in the presence of multiple growth factors, SMC undergo a phenotype switch characterized by the loss of contractile markers and appearance of expression of non-muscle proteins (“proliferative phenotype”). While a number of factors have been reported to modulate this process, its regulation remains uncertain. Here we show that induction of SMC FGF signaling inhibits TGFβ signaling and converts contractile SMCs to the proliferative phenotype. Conversely, inhibition of SMC FGF signaling induces TGFβ signaling converting proliferating SMCs to the contractile phenotype, even in the presence of various growth factors in vitro or vascular injury in vivo. The importance of this signaling cross-talk is supported by in vivo data that show that an SMC deletion of a pan-FGF receptor adaptor Frs2α (fibroblast growth factor receptor substrate 2 alpha) in mice profoundly reduces neointima formation and vascular remodelling following carotid artery ligation. These results demonstrate that FGF-TGFβ signaling antagonism is the primary regulator of the SMC phenotype switch. Manipulation of this cross-talk may be an effective strategy for treatment of SMC-proliferation related diseases.
format Online
Article
Text
id pubmed-5025753
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-50257532016-09-22 Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation Chen, Pei-Yu Qin, Lingfeng Li, Guangxin Tellides, George Simons, Michael Sci Rep Article Smooth muscle cells (SMCs) in normal blood vessels exist in a highly differentiate state characterized by expression of SMC-specific contractile proteins (“contractile phenotype”). Following blood vessel injury in vivo or when cultured in vitro in the presence of multiple growth factors, SMC undergo a phenotype switch characterized by the loss of contractile markers and appearance of expression of non-muscle proteins (“proliferative phenotype”). While a number of factors have been reported to modulate this process, its regulation remains uncertain. Here we show that induction of SMC FGF signaling inhibits TGFβ signaling and converts contractile SMCs to the proliferative phenotype. Conversely, inhibition of SMC FGF signaling induces TGFβ signaling converting proliferating SMCs to the contractile phenotype, even in the presence of various growth factors in vitro or vascular injury in vivo. The importance of this signaling cross-talk is supported by in vivo data that show that an SMC deletion of a pan-FGF receptor adaptor Frs2α (fibroblast growth factor receptor substrate 2 alpha) in mice profoundly reduces neointima formation and vascular remodelling following carotid artery ligation. These results demonstrate that FGF-TGFβ signaling antagonism is the primary regulator of the SMC phenotype switch. Manipulation of this cross-talk may be an effective strategy for treatment of SMC-proliferation related diseases. Nature Publishing Group 2016-09-16 /pmc/articles/PMC5025753/ /pubmed/27634335 http://dx.doi.org/10.1038/srep33407 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chen, Pei-Yu
Qin, Lingfeng
Li, Guangxin
Tellides, George
Simons, Michael
Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation
title Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation
title_full Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation
title_fullStr Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation
title_full_unstemmed Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation
title_short Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation
title_sort fibroblast growth factor (fgf) signaling regulates transforming growth factor beta (tgfβ)-dependent smooth muscle cell phenotype modulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025753/
https://www.ncbi.nlm.nih.gov/pubmed/27634335
http://dx.doi.org/10.1038/srep33407
work_keys_str_mv AT chenpeiyu fibroblastgrowthfactorfgfsignalingregulatestransforminggrowthfactorbetatgfbdependentsmoothmusclecellphenotypemodulation
AT qinlingfeng fibroblastgrowthfactorfgfsignalingregulatestransforminggrowthfactorbetatgfbdependentsmoothmusclecellphenotypemodulation
AT liguangxin fibroblastgrowthfactorfgfsignalingregulatestransforminggrowthfactorbetatgfbdependentsmoothmusclecellphenotypemodulation
AT tellidesgeorge fibroblastgrowthfactorfgfsignalingregulatestransforminggrowthfactorbetatgfbdependentsmoothmusclecellphenotypemodulation
AT simonsmichael fibroblastgrowthfactorfgfsignalingregulatestransforminggrowthfactorbetatgfbdependentsmoothmusclecellphenotypemodulation