Mechanosensitive Channel PIEZO1 Senses Shear Force to Induce KLF2/4 Expression Via CaMKII/MEKK3/ERK5 Axis in Endothelial Cells

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Jul 27

PMID 35883633

Authors

Qi Zheng

Yonggang Zou

Peng Teng

Zhenghua Chen

Yuefeng Wu

Xiaoyi Dai

Xiya Li

Zonghao Hu

Shengjun Wu

Yanhua Xu

Weiguo Zou

Hai Song

Liang Ma

Affiliations

Soon will be listed here.

Abstract

Shear stress exerted by the blood stream modulates endothelial functions through altering gene expression. KLF2 and KLF4, the mechanosensitive transcription factors, are promoted by laminar flow to maintain endothelial homeostasis. However, how the expression of KLF2/4 is regulated by shear stress is poorly understood. Here, we showed that the activation of PIEZO1 upregulates the expression of KLF2/4 in endothelial cells. Mice with endothelial-specific deletion of exhibit reduced KLF2/4 expression in thoracic aorta and pulmonary vascular endothelial cells. Mechanistically, shear stress activates PIEZO1, which results in a calcium influx and subsequently activation of CaMKII. CaMKII interacts with and activates MEKK3 to promote MEKK3/MEK5/ERK5 signaling and ultimately induce the transcription of . Our data provide the molecular insight into how endothelial cells sense and convert mechanical stimuli into a biological response to promote KLF2/4 expression for the maintenance of endothelial function and homeostasis.

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