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Sci Rep. 2016 Sep 16;6:33407. doi: 10.1038/srep33407.

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

Author information

1
Yale Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
2
Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
3
Department of Vascular Surgery, The First Hospital of China Medical University, 155 Nanjing Bei Street, Shenyang, China.
4
Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.

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.

PMID:
27634335
PMCID:
PMC5025753
DOI:
10.1038/srep33407
[Indexed for MEDLINE]
Free PMC Article

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