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

Content Provider	Semantic Scholar
Author	Chen, Pei-yu Qin, Lingfeng Li, Guangxin Tellides, George Simons, Michael
Copyright Year	2016
Abstract	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.
Starting Page	767
Ending Page	801
Page Count	35
File Format	PDF HTM / HTML
PubMed reference number	27634335
Alternate Webpage(s)	https://doi.org/10.1038/srep33407
DOI	10.1038/srep33407
Journal	Scientific reports
Volume Number	6
Language	English
Access Restriction	Open
Subject Keyword	Adrenergic beta-Antagonists Blood Vessel Tissue Carotid Arteries Contractile Proteins Cross Reactions Cross-Talk Deletion Mutation FRS2 protein, human Fibroblast Growth Factor Receptors In Vitro [Publication Type] Ligation Muscle Cells Myalgia Myocytes, Smooth Muscle Neointima Smooth muscle (tissue) Transforming Growth Factors Vascular System Injuries subrhabdomeral cisterna
Content Type	Text
Resource Type	Article