Mechanical stretch promotes hypertrophic scar formation through mechanically activated cation channel Piezo1

Cell Death Dis. 2021 Mar 1;12(3):226. doi: 10.1038/s41419-021-03481-6.

Abstract

Hypertrophic scar (HS) formation is a skin fibroproliferative disease that occurs following a cutaneous injury, leading to functional and cosmetic impairment. To date, few therapeutic treatments exhibit satisfactory outcomes. The mechanical force has been shown to be a key regulator of HS formation, but the underlying mechanism is not completely understood. The Piezo1 channel has been identified as a novel mechanically activated cation channel (MAC) and is reportedly capable of regulating force-mediated cellular biological behaviors. However, the mechanotransduction role of Piezo1 in HS formation has not been investigated. In this work, we found that Piezo1 was overexpressed in myofibroblasts of human and rat HS tissues. In vitro, cyclic mechanical stretch (CMS) increased Piezo1 expression and Piezo1-mediated calcium influx in human dermal fibroblasts (HDFs). In addition, Piezo1 activity promoted HDFs proliferation, motility, and differentiation in response to CMS. More importantly, intradermal injection of GsMTx4, a Piezo1-blocking peptide, protected rats from stretch-induced HS formation. Together, Piezo1 was shown to participate in HS formation and could be a novel target for the development of promising therapies for HS formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Calcium Signaling* / drug effects
  • Case-Control Studies
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Cicatrix, Hypertrophic / genetics
  • Cicatrix, Hypertrophic / metabolism*
  • Cicatrix, Hypertrophic / pathology
  • Cicatrix, Hypertrophic / prevention & control
  • Disease Models, Animal
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Ion Channels / antagonists & inhibitors
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Male
  • Mechanotransduction, Cellular* / drug effects
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Modulators / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Skin / drug effects
  • Skin / metabolism*
  • Skin / pathology
  • Spider Venoms / pharmacology

Substances

  • Intercellular Signaling Peptides and Proteins
  • Ion Channels
  • MTx4 protein, Grammostola spatulata
  • Membrane Proteins
  • Membrane Transport Modulators
  • PIEZO1 protein, human
  • Piezo1 protein, rat
  • Spider Venoms