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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. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hhmore » signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.« less

Authors:
 [1];  [1];  [2]; ; ; ; ;  [1];  [3];  [4];  [1];  [1];  [1]
  1. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)
  2. (China)
  3. Wenzhou People's Hospital, Wenzhou, Zhejiang (China)
  4. Ningbo First Hospital, Ningbo, Zhejiang (China)
Publication Date:
OSTI Identifier:
22649858
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 355; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; FIBROBLASTS; GENES; GROWTH FACTORS; HEALING; PHOSPHOTRANSFERASES; POLYMERASE CHAIN REACTION; RNA; SKIN; THERAPY; TRANSLOCATION; WOUNDS

Citation Formats

Zhu, Zhong Xin, Sun, Cong Cong, Wenzhou People's Hospital, Wenzhou, Zhejiang, Ting Zhu, Yu, Wang, Ying, Wang, Tao, Chi, Li Sha, Cai, Wan Hui, Zheng, Jia Yong, Zhou, Xuan, Cong, Wei Tao, Li, Xiao Kun, E-mail: proflxk@163.com, and Jin, Li Tai, E-mail: jin_litai@126.com. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.03.054.
Zhu, Zhong Xin, Sun, Cong Cong, Wenzhou People's Hospital, Wenzhou, Zhejiang, Ting Zhu, Yu, Wang, Ying, Wang, Tao, Chi, Li Sha, Cai, Wan Hui, Zheng, Jia Yong, Zhou, Xuan, Cong, Wei Tao, Li, Xiao Kun, E-mail: proflxk@163.com, & Jin, Li Tai, E-mail: jin_litai@126.com. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration. United States. doi:10.1016/J.YEXCR.2017.03.054.
Zhu, Zhong Xin, Sun, Cong Cong, Wenzhou People's Hospital, Wenzhou, Zhejiang, Ting Zhu, Yu, Wang, Ying, Wang, Tao, Chi, Li Sha, Cai, Wan Hui, Zheng, Jia Yong, Zhou, Xuan, Cong, Wei Tao, Li, Xiao Kun, E-mail: proflxk@163.com, and Jin, Li Tai, E-mail: jin_litai@126.com. Thu . "Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration". United States. doi:10.1016/J.YEXCR.2017.03.054.
@article{osti_22649858,
title = {Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration},
author = {Zhu, Zhong Xin and Sun, Cong Cong and Wenzhou People's Hospital, Wenzhou, Zhejiang and Ting Zhu, Yu and Wang, Ying and Wang, Tao and Chi, Li Sha and Cai, Wan Hui and Zheng, Jia Yong and Zhou, Xuan and Cong, Wei Tao and Li, Xiao Kun, E-mail: proflxk@163.com and Jin, Li Tai, E-mail: jin_litai@126.com},
abstractNote = {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. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.},
doi = {10.1016/J.YEXCR.2017.03.054},
journal = {Experimental Cell Research},
number = 2,
volume = 355,
place = {United States},
year = {Thu Jun 15 00:00:00 EDT 2017},
month = {Thu Jun 15 00:00:00 EDT 2017}
}