LIMK2 inactivation suppresses mechanical stimulation-induced dermal fibroblast differentiation and resistance to apoptosis

LIMK2失活抑制机械刺激诱导的真皮成纤维细胞分化和抗凋亡能力

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Abstract

Abnormal scar formation is a clinical challenge with limited therapeutic options. Mechanical stimulation is implicated in abnormal scarring. Accordingly, the present study investigated the role of LIMK2, a component of the Rho/ROCK/LIMK/cofilin pathway, in cell differentiation and apoptosis in response to mechanical stimulation and proliferation in human dermal fibroblasts (HDFs). In normal HDFs, expression of α-smooth muscle actin (α-SMA), a marker of differentiation into myofibroblasts, significantly increased with mechanical stimulation; however, this change was not observed when LIMK2 was inactivated. Mechanical stimulation increased expression of the anti-apoptotic protein Bcl-2 and decreased that of the pro-apoptotic protein BAX in controls, but these effects were not observed with LIMK2 inactivation. Moreover, fibroblast proliferation was inhibited with LIMK2 inactivation. These findings suggest that LIMK2 inactivation suppresses mechanical stimulation-induced myofibroblast differentiation and resistance to apoptosis, and also inhibits HDF proliferation, highlighting LIMK2 as a potential therapeutic target for the prevention and treatment of abnormal scars.

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