title: 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.
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhong Xin
authors.initials: ZX
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; Wenzhou People's Hospital, Wenzhou, Zhejiang, China.
authors.forename: Cong Cong
authors.initials: CC
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ting Zhu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Li Sha
authors.initials: LS
authors.lastname: Chi
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Wan Hui
authors.initials: WH
authors.lastname: Cai
authors.affiliation: Wenzhou People's Hospital, Wenzhou, Zhejiang, China.
authors.forename: Jia Yong
authors.initials: JY
authors.lastname: Zheng
authors.affiliation: Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Wei Tao
authors.initials: WT
authors.lastname: Cong
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: proflxk@163.com.
authors.forename: Xiao Kun
authors.initials: XK
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: jin_litai@126.com.
authors.forename: Li Tai
authors.initials: LT
authors.lastname: Jin
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D016222:Fibroblast Growth Factor 2
keywords: Fibroblast migration; Hedgehog pathway; Skin wound healing; bFGF; β-catenin