Fibroblasts and myofibroblasts in wound healing

Abstract

(Myo)fibroblasts are key players for maintaining skin homeostasis and for orchestrating physiological tissue repair. (Myo)fibroblasts are embedded in a sophisticated extracellular matrix (ECM) that they secrete, and a complex and interactive dialogue exists between (myo)fibroblasts and their microenvironment. In addition to the secretion of the ECM, (myo)fibroblasts, by secreting matrix metalloproteinases and tissue inhibitors of metalloproteinases, are able to remodel this ECM. (Myo)fibroblasts and their microenvironment form an evolving network during tissue repair, with reciprocal actions leading to cell differentiation, proliferation, quiescence, or apoptosis, and actions on growth factor bioavailability by binding, sequestration, and activation. In addition, the (myo)fibroblast phenotype is regulated by mechanical stresses to which they are subjected and thus by mechanical signaling. In pathological situations (excessive scarring or fibrosis), or during aging, this dialogue between the (myo)fibroblasts and their microenvironment may be altered or disrupted, leading to repair defects or to injuries with damaged and/or cosmetic skin alterations such as wrinkle development. The intimate dialogue between the (myo)fibroblasts and their microenvironment therefore represents a fascinating domain that must be better understood in order not only to characterize new therapeutic targets and drugs able to prevent or treat pathological developments but also to interfere with skin alterations observed during normal aging or premature aging induced by a deleterious environment.

α-SMA Expression Increased Over Cell Passages and Decreased by Exogenous TGF-β1, In Vitro Studies on Myofibroblast Derived from Orbital Socket Contracture

“…[19] During physiological wound healing process, myofibroblasts undergo apoptosis. [20,21,22,23]. On the contrary, the addition of exogenous TGF-β1 on passage 3 resulted in significantly low α-SMA.…”

Basic Fibroblast Growth Factor Influences Epidermal Homeostasis of Living Skin Equivalents through Affecting Fibroblast Phenotypes and Functions

“…However, the fibroblasts from different compartments of the dermis or of different passages may possess distinct characteristics and therefore affect epidermal homeostasis [14, 15]. During skin wound healing, dermal fibroblasts may adopt different phenotypes, α-SMA positive (myofibroblasts) or negative, under the influence of a complex of growth factors and cytokines (especially TGF-β 1 ), and function differently [16, 17]. bFGF is capable of keeping α-SMA fibroblasts negative by suppressing α-SMA expression or inducing the apoptosis of myofibroblasts which are conventionally marked by the expression of α-SMA [6, 18].…”

Topical Application of Hesperidin, a Citrus Bioflavanone Accelerates Healing of Full Thickness Dermal Excision Wounds in Mice Exposed to 6 Gy of Whole Body Γ-Radiation

“…Further, wound contraction of open excision wounds has been found to be a function of contractile fibroblasts, known as myofibroblasts [52,53] that are adversely affected by irradiation as ionizing radiations produce cytotoxic effect on fibroblasts and impair wound healing [14,54]. The killing of fibroblasts, known as myofibroblasts will also have negative effect on extracellular matrix deposition impairing the wound healing.…”