Microenvironment-induced myofibroblast-like conversion of engrafted keratinocytes

Abstract

Myofibroblasts, recognized classically by -smooth muscle actin (-SMA) expression, play a key role in the wound-healing process, promoting wound closure and matrix deposition. Although a body of evidence shows that keratinocytes explanted onto a wound bed promote closure of a skin injury, the underlying mechanisms are not well understood. The basal layer of epidermis is rich in undifferentiated keratinocytes (UKs). We showed that UKs injected into granulation tissue could switch into -SMA positive cells, and accelerate the rate of skin wound healing. In addition, when the epidermis sheets isolated from foreskin cover up the wound bed or are induced in vitro, keratinocytes located at the basal layers or adjacent sites were observed to convert into myofibroblast-like cells. Thus, UKs have a potential for myofibroblastic transition, which provides a novel mechanism by which keratinocyte explants accelerate skin wound healing. epithelial-mesenchymal transition, epithelial-myofibroblast transition, keratinocyte-myofibroblast transition, myofibroblast, wound healing Citation:Li MR, Ti DD, Han WD, Fu XB. Microenvironment-induced myofibroblast-like conversion of engrafted keratinocytes.

P311 induces the transdifferentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor β1 expression

“…Furthermore, the mesenchymal features of these cells were reduced in the P311 KO mouse burn wounds. In this study, we found that superficial second-degree thermal burn wounds in mice healed within 10 days and α-SMA + cells were not detected in the epidermis of these mice, consistent with the results of previous studies [14, 15]. However, the burn wounds obtained from patients who needed skin graft surgery healed slower than the mouse wounds, and α-SMA + cells were observed in the wounds of these patients.…”

“…In skin, epidermal cells are classically thought to perform their role in myofibroblast formation by secreting transforming growth factor beta 1 (TGFβ1), interleukin-1 (IL-1), basic fibroblast growth factor (bFGF), tumor necrosis factor alpha (TNFα), and other humoral factors that regulate the fibroblast to myofibroblast differentiation [11–13]. Recently, several studies have shown that epidermal keratinocytes directly transdifferentiate into fibroblasts when exposed to TGFβ1, IL-1β, TNFα, and fetal bovine serum (FBS) [14–16]. However, the mechanisms involved in keratinocyte transdifferentiation during wound healing are not fully understood.…”

Cutaneous involvement in luteinized thecomas with sclerosing peritonitis (LTSP)—A new finding in a rare syndrome

“…As in previous studies, a subset of intestinal subserosal LMW‐CK (+)/vimentin (+)/SMA (+) fibroblasts was observed, potentially indicating transformation of the mesothelial cavitary lining to subserosal fibroblasts (mesothelial‐mesenchymal transition) . Interestingly, the unusual pattern of SMA positivity in the basal layer, seen in 2 skin biopsies, raises the possibility of cutaneous epithelial‐mesenchymal transition (EMT), supporting the theory that stimulated basal keratinocytes are capable of myofibroblastic differentiation . Although artefactual staining cannot be excluded, the lack of keratinocyte staining with SMA in control tissue or other skin biopsies and the membranous staining pattern characteristic of true SMA positivity does not favor this.…”

TLR3 activation induces S100A7 to regulate keratinocyte differentiation after skin injury

“…An efficient re-epithelialization is required for wound repair (Eckert et al, 2002). In the skin, re-epithelialization is accomplished by keratinocyte proliferation, migration, stratification, and differentiation (Laplante et al, 2001;Li et al, 2014). Among these, the proliferation and differentiation of keratinocytes enable skin stratification, thus promoting wound closure and forming a physical barrier (Lee et al, 2006).…”