Current progress in understanding the molecular pathogenesis of burn scar contracture

Abstract

Abnormal wound healing is likely to induce scar formation, leading to dysfunction, deformity, and psychological trauma in burn patients. Despite the advancement of medical care treatment, scar contracture in burn patients remains a challenge. Myofibroblasts play a key role in scar contracture. It has been demonstrated that myofibroblasts, as well as inflammatory cells, fibroblasts, endothelial cells, and epithelial cells, secrete transforming growth factor-β1 (TGF-β1) and other cytokines, which can promote persistent myofibroblast activation via a positive regulation loop. In addition to the cellular contribution, the microenvironments, including the mechanical tension and integrin family, are also involved in scar contracture. Most recently, eukaryotic initiation factor 6 (eIF6), an upstream regulator of TGF-β1, has been demonstrated to be involved in myofibroblast differentiation and contraction in both in vitro fibroblast-populated collagen lattice (FPCL) and in vivo external mechanical stretch models. Moreover, the data showed that P311 could induce the transdifferentiation of epidermal stem cells to myofibroblasts by upregulating TGF-β1 expression, which mediated myofibroblast contraction. In this review, we briefly described the most current progress on the biological function of myofibroblasts in scar contracture and subsequently summarized the molecular events that initiated contracture. This would help us better understand the molecular basis of scar contracture as well as to find a comprehensive strategy for preventing/managing scar contracture.

Immune Regulation of Skin Wound Healing: Mechanisms and Novel Therapeutic Targets

“…Interestingly, Tcell-deficient athymic nude-nu mice also heal with minimal scarring. [82][83] Role of neutrophils in skin scarring. Potentially because they only participate in the earliest stages of wound healing, few studies have looked at the role of neutrophils in dermal scarring and they are believed to have a negligible long-term impact.…”

Toward understanding scarless skin wound healing and pathological scarring

“…The mechanical microenvironment affects scar contracture, and if the contraction continues after healing, it results in a poor functional and cosmetic outcome 2, 3, 34, 36 . Fibroblasts are sensitive to exogenous mechanical forces, which trigger the upregulation of several fibrotic genes, encoding proteins such as TGFβ, αSMA and collagen I, through different mechanoreceptors such as integrins, growth factor receptors, G protein–coupled receptors and ion channels 2, 37 . The cellular contractile forces in the activated myofibroblasts are critical to maintain scar contracture through their adhesion to the ECM.…”

Predictable fibroblast tension generation by measuring compaction of anchored collagen matrices using microscopy and optical coherence tomography

“…Wound healing, Dupuytren's contracture, and burn scars have in common connective tissue remodeling and contraction by fibroblasts, leading to the myofibroblast phenotype presence [1][2][3]. Fibroblasts in vivo use migratory properties to reorganize the collagen and generate sufficient tension so that myofibroblasts can differentiate [4].…”