Mechanical Stretch Triggers Epithelial-Mesenchymal Transition in Keratinocytes Through Piezo1 Channel

Jiahao He; Shengzhou Shan; Qingfeng Li; Bin Fang; Yun Xie

doi:10.3389/fphys.2022.745572

Mechanical Stretch Triggers Epithelial-Mesenchymal Transition in Keratinocytes Through Piezo1 Channel

Front Physiol. 2022 May 9:13:745572. doi: 10.3389/fphys.2022.745572. eCollection 2022.

Authors

Jiahao He¹, Shengzhou Shan¹, Qingfeng Li¹, Bin Fang¹, Yun Xie¹

Affiliation

¹ Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

The epithelial-mesenchymal transition (EMT) process has emerged as a central regulator of embryonic development, tissue repair and tumor malignancy. In recent years, researchers have specifically focused on how mechanical signals drive the EMT program in epithelial cells. However, how epithelial cells specifically leverage mechanical force to control the EMT process remains unclear. Here, we show that the bona fide mechanically activated cation channel Piezo1 plays a critical role in the EMT. The Piezo1 is expressed in human primary epidermal keratinocytes (HEKs) and is responsible for the mechanical stretch-induced Ca²⁺ concentration. Inhibition of Piezo1 activation by the inhibitor GsMTx4 or by siRNA-mediated Piezo1 knockdown influenced the morphology and migration of HEKs. Moreover, Piezo1 activity also altered EMT-correlated markers expression in response to mechanical stretch. We propose that the mechanically activated cation channel Piezo1 is an important determinant of mechanical force-induced EMT in keratinocytes and might play similar roles in other epithelial cells.

Keywords: Piezo1; epithelial physiology; epithelial-mesenchymal transition; keratinocyte; mechanical force.