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.
Highlights
Hypertrophic scar (HS) formation is a skin fibroproliferative disease that occurs following a cutaneous injury, inducing severe functional and esthetic disability[1]
Piezo[1] expression is increased in human and rat HS tissues First, we analyzed the expression of Piezo[1] and Piezo[2] in human dermal fibroblasts (HDFs)
To further determine whether dermal fibroblasts show a high expression of Piezo[1], we performed co-staining for α-SMA with Piezo[1] to evaluate their co-localization in human HS tissues
Summary
Hypertrophic scar (HS) formation is a skin fibroproliferative disease that occurs following a cutaneous injury, inducing severe functional and esthetic disability[1]. Official journal of the Cell Death Differentiation Association He et al Cell Death and Disease (2021)12:226 mechanosensors that directly detect and transduce scar tissue mechanics to modulate HS formation remain to be completely identified. A stiffer scar tissue establishes a “vicious feedback loop” that continuously stimulates fibroblasts overactivation and collagen production, further contributing to HS progression and contraction[24]. It is unknown whether the aberrant mechanical microenvironment in the scar interplays with the mechanosensory function of Piezo[1] to regulate dermal fibroblasts activity, resulting in HS formation. We postulated that the Piezo[1] channel might be a key mediator involved in the induction of HS development by mechanical signals
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
