Abstract
Hypertrophic scars (HTS), the excessive deposition of scar tissue by fibroblasts, is one of the most common skin disorders. Fibroblasts derived from surgical scar tissue produce high levels of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1). However, the molecular mechanisms for this phenomenon is poorly understood. Thus, the purpose of this study was to evaluate the molecular mechanisms of HTS and their potential therapeutic implications. Fibroblasts derived from skin HTS were cultured and characterized in vitro. The fibroblasts were synchronized and randomly assigned to two groups: cyclic stretch and cyclic stretch pre-treated with SB203580 (a p38MAPK inhibitor). Cyclic stretch at 10% strain was applied at a loading frequency of 10 cycles per minute (i.e. 5 seconds of tension and 5 seconds of relaxation) for 0 h, 6 h and 12 h. Cyclic stretch on HTS fibroblasts led to an increase in the expression of α-SMA and TGF-β1 mRNA and protein and the phosphorylation of p38MAPK. SB203580 reversed these effects and caused a decrease in matrix contraction. Furthermore, HTS fibroblast growth was partially blocked by p38MAPK inhibition. Therefore, the mechanism of cyclic stretch involves p38 MAPK, and its inhibition is suggested as a novel therapeutic strategy for HTS.
Highlights
Hypertrophic scars (HTS) are a common clinical pathological state
We examined the in vitro effect of cyclic stretch on the p38MAPK signal transduction pathway and transdifferentiation of fibroblasts derived from primary human HTS
MFBs are responsible for the excessive deposition and irreversible remodeling of the extracellular matrix (ECM), which is a hallmark of virtually all fibrotic diseases and impedes organ function, often leading to lethal organ failure [29]
Summary
Hypertrophic scars (HTS) are a common clinical pathological state. They are characterized by the proliferation of a large number of fibroblasts, excessive deposition of extracellular matrix (ECM) and microvascular dysplasia with infiltration of inflammatory cells [1]. HTS show excess accumulation of collagen fiber bundles, with a high density of endothelial cells, fibroblasts and myofibroblasts (MFB) [2]. Fibroblasts are an important type of cells that are related to fibrillogenesis and wound healing. In scarless or regenerative healing, fibroblasts are quiescent and do not significantly proliferate, but provide enough ECM synthesis to maintain adequate tissue strength. Fibroblast activation leads to cell proliferation and ECM synthesis, reducing collagen remodeling
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