Roles of Mechanosensitive Channel Piezo1 in Wound Healing and Scar Formation

Abstract

The ability to heal one's wounds is perhaps one of the most fundamental and critical of physiologic processes. This coordinated and closely regulated sequential biological process involves a variety of migratory and resident cells. The activation, modulation, balance, and control of these functions depend upon soluble mediators that activate cells and modulate their diverse functions. Recent advances have identified mechanotransduction as functionally integral in many different cell types and physiologic processes. The mechanically sensitive ion channel Pieoz1 is expressed on platelets, neutrophils, macrophages, endothelial cells, keratinocytes, and fibroblasts, all of which are principally involved in wound healing. On a cellular level, there have been great advances in our understanding of the functional role of Piezo1 mechanotransduction in cutaneous wounding. The blocking of Piezo1 has recently been shown to reduce scarring in vivo and yet, thus far, a comprehensive understanding of the roles that Piezo1 plays in in vivo wound healing remains lacking. Recognizing the ever-present and critical importance of optimal and reparative wound healing, and with the availability of new physical mechanomodulating devices, the time is ripe for gaining deeper insights into optimizing wound healing. In this review, we describe the current knowledge of Piezo1 related to wound healing.

Keywords: Piezo1; ion channel; mechanobiology; scar; wound healing.

Figure 1

Schematic illustration of Piezo1 as visualized from the top (extracellular) view. The three C-terminal extracellular domains that form the cap (black) and the three-bladed propeller subunits (orange) are depicted (adapted from [35]).

Figure 2

Mechanotransduction (by various modes; see Figure 3) resulting in opening of the pore with resultant calcium flux: (a) closed Piezo1 channel; (b) open Piezo1 channel (adapted from [36]).

Figure 3

Piezo1 mechanotransduction in wound-related cells and associated force relationships, which have been described as opening the Piezo1 ion channel.