Cell Communication and Signaling | |
Extracellular matrix stiffness mediates uterine repair via the Rap1a/ARHGAP35/RhoA/F-actin/YAP axis | |
Research | |
Ruiting Hu1  Chunyang Han1  Yan Wang1  Tao Zhang2  Shuai Guo3  Zhimin Wu3  Changwei Qiu3  Ganzhen Deng3  Junfeng Liu4  | |
[1] College of Animal Science and Technology, Anhui Agricultural University, 230031, Hefei, People’s Republic of China;College of Animal Science and Technology, Anhui Agricultural University, 230031, Hefei, People’s Republic of China;Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, 430070, Wuhan, People’s Republic of China;Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, 430070, Wuhan, People’s Republic of China;Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, 430070, Wuhan, People’s Republic of China;College of Animal Science and Technology, Tarim University, 843300, Alar, Xinjiang, People’s Republic of China; | |
关键词: Mechanotransduction; Hippo-YAP; Uterine repair; ECM stiffness; Rap1a; | |
DOI : 10.1186/s12964-022-01018-8 | |
received in 2022-10-27, accepted in 2022-12-14, 发布年份 2022 | |
来源: Springer | |
【 摘 要 】
The integrity of the structure and function of the endometrium is essential for the maintenance of fertility. However, the repair mechanisms of uterine injury remain largely unknown. Here, we showed that the disturbance of mechanical cue homeostasis occurs after uterine injury. Applying a multimodal approach, we identified YAP as a sensor of biophysical forces that drives endometrial regeneration. Through protein activation level analysis of the combinatorial space of mechanical force strength and of the presence of particular kinase inhibitors and gene silencing reagents, we demonstrated that mechanical cues related to extracellular matrix rigidity can turn off the Rap1a switch, leading to the inactivation of ARHGAP35and then induced activation of RhoA, which in turn depends on the polymerization of the agonist protein F-actin to activate YAP. Further study confirmed that mechanotransduction significantly accelerates remodeling of the uterus by promoting the proliferation of endometrial stromal cells in vitro and in vivo. These studies provide new insights into the dynamic regulatory mechanisms behind uterine remodeling and the function of mechanotransduction.B4ojxzzgfZhteej7Gc57h4Video Abstract
【 授权许可】
CC BY
© The Author(s) 2023
【 预 览 】
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