Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration.

Abstract:

:Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy.

journal_name

Exp Cell Res

authors

Zhu ZX,Sun CC,Ting Zhu Y,Wang Y,Wang T,Chi LS,Cai WH,Zheng JY,Zhou X,Cong WT,Li XK,Jin LT

doi

10.1016/j.yexcr.2017.03.054

subject

Has Abstract

pub_date

2017-06-15 00:00:00

pages

83-94

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(17)30181-7

journal_volume

355

pub_type

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