伤口愈合
细胞生物学
化学
连环素
磷酸化
基因敲除
癌症研究
成纤维细胞
细胞迁移
信号转导
Wnt信号通路
体外
生物
免疫学
生物化学
基因
作者
Nan Wang,Xiejun Xu,Fangqian Guan,Yeyi Zheng,Yanni Shou,Tianpeng Xu,Guang Xian Shen,Hui Chen,Yifan Lin,Weitao Cong,Litai Jin,Zhongxin Zhu
标识
DOI:10.1096/fj.202302251r
摘要
Abstract Skin wound healing is a complex and organized biological process, and the dermal fibroblasts play a crucial role. α‐Catenin is known to be involved in regulating various cellular signals, and its role in wound healing remains unclear. Here, we have identified the pivotal role of the α‐catenin/FAK/YAP signaling axis in the proliferation and migration of dermal fibroblasts, which contributes to the process of skin wound healing. Briefly, when α‐catenin was knocked down specifically in dermal fibroblasts, the wound healing rate is significantly delayed. Moreover, interfering with α‐catenin can impede the proliferation and migration of dermal fibroblasts both in vitro and in vivo. Mechanistically, the overexpression of α‐catenin upregulates the nuclear accumulation of YAP and transcription of downstream target genes, resulting in enhanced the proliferation and migration of dermal fibroblasts. Furthermore, the FAK Tyr397 phosphorylation inhibitor blocked the promoting effects of α‐catenin on YAP activation. Importantly, the continuous phosphorylation mutation of FAK Tyr397 reversed the retardatory effects of α‐catenin knockdown on wound healing, by increasing the vitality of fibroblasts. Likewise, α‐catenin/FAK was validated as a therapeutic target for wound healing in the db/db chronic trauma model. In summary, our findings have revealed a novel mechanism by which α‐catenin facilitates the function of fibroblasts through the activity of the FAK/YAP signaling axis. These findings define a promising therapeutic strategy for accelerating the wound healing process.
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