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

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.

Automated summary

The study identified that Piezo1 channel is overexpressed in myofibroblasts of hypertrophic scar (HS) tissues and plays a regulatory role in fibroblasts, thus participating in HS formation. Piezo1 activity enhances various cellular biological behaviors in response to mechanical stretch in dermal fibroblasts, including proliferation, motility, and differentiation. Additionally, blocking Piezo1 with GsMTx4 peptide injection protected rats from stretch-induced HS formation, suggesting Piezo1 as a potential therapeutic target for HS.