English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Mechano-signaling via Piezo1 prevents activation and p53-mediated senescence of muscle stem cells

Peng, Y., Du, J., Gunther, S., Guo, X., Wang, S., Schneider, A., et al. (2022). Mechano-signaling via Piezo1 prevents activation and p53-mediated senescence of muscle stem cells. REDOX BIOLOGY, 52: 102309. doi:10.1016/j.redox.2022.102309.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Peng, Yundong1, Author              
Du, Jingjing1, Author              
Gunther, Stefan1, Author              
Guo, Xinyue1, Author              
Wang, Shengpeng2, Author              
Schneider, Andre1, Author              
Zhu, Li, Author
Braun, Thomas1, Author              
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              
2Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

Content

show
hide
Free keywords: -
 Abstract: Skeletal muscle stem cells (MuSCs), also called satellite cells, are instrumental for postnatal muscle growth and skeletal muscle regeneration. Numerous signaling cascades regulate the fate of MuSCs during muscle regeneration but the molecular mechanism by which MuSCs sense mechanical stimuli remain unclear. Here, we describe that Piezo1, a mechanosensitive ion channel, keeps MuSCs in a quiescent state and prevents senescence. Absence of Piezo1 induces precocious activation of MuSCs, attenuates proliferation, and impairs differentiation, essentially abolishing efficient skeletal muscle regeneration and replenishment of the MuSC pool. Furthermore, we discovered that inactivation of Piezo1 results in compensatory up-regulation of T-type voltage-gated Ca2+ channels, leading to increased Ca-2+ influx, which strongly induces NOX4 expression via cPKC. Elevated NOX4 expression in Piezo1-deficient MuSCs increases ROS levels and DNA damage, causing P53-dependent cellular senescence and cell death. The importance of the P53/P21-axis for mediating Piezo1-dependent cellular defects was confirmed by pharmacological inhibition of P53 in Piezo1-deficient mice, which abrogates increased senescence of muscle cells and normalizes muscle regeneration. Our findings uncover an essential role of Piezo1mediated mechano-signaling in MuSCs for maintaining quiescence and preventing senescence. Reduced mechano-signaling due to decreased physical activity during aging may contribute to the increase of senescent cells and the decline of MuSC numbers in geriatric mice and humans.

Details

show
hide
Language(s):
 Dates: 2022-04-02
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: REDOX BIOLOGY
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 52 Sequence Number: 102309 Start / End Page: - Identifier: ISSN: 2213-2317