Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration
Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration
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Hedgehog 信号传导有助于碱性成纤维细胞生长因子调节的成纤维细胞迁移
DOI：
10.1016/j.yexcr.2017.03.054
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发表时间：
2017
影响因子：
3.7
通讯作者：
Jin Li Tai
中科院分区：
文献类型：
--
作者：
Zhu Zhong Xin;Sun Cong Cong;Zhu Yu Ting;Wang Ying;Wang Tao;Chi Li Sha;Cai Wan Hui;Zheng Jia Yong;Zhou Xuan;Cong Wei Tao;Li Xiao Kun;Jin Li Tai
成纤维细胞迁移是皮肤伤口愈合的中心过程，需要多种类型的生长因子的协调。碱性成纤维细胞生长因子（bFGF）是一种著名的成纤维细胞生长因子（FGF），能够加速成纤维细胞迁移;然而，bFGF调节成纤维细胞迁移的潜在机制仍不清楚。通过RNA-seq分析，我们已经确定了hedgehog（Hh）经典途径基因，包括Smothened（Smo）和Gli 1，受到bFGF的调控。进一步的分析表明，通过上调Smo激活Hh通路促进成纤维细胞迁移、侵袭和皮肤伤口愈合，但GANT 61（Gli 1/Gli 2的选择性拮抗剂）显著降低了Hh通路。Western blot分析和siRNA转染实验表明Smo作用于磷脂酰肌醇3-激酶（PI 3 K）-c-Jun N-末端激酶（JNK）-β-catenin的上游，促进细胞迁移。此外，RNA-seq和qRT-PCR分析显示，Hh通路基因包括Smo和Gli 1都在β-catenin的控制下，表明β-catenin反过来反馈激活Hh信号传导。总而言之，我们的分析确定了一种新的bFGF调节机制，Hh信号通过该机制调节人类成纤维细胞迁移，这里提供的数据为伤口愈合治疗开辟了一条新途径。
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.