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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The datasets generated and/or analyzed during the present study are available from the corresponding author on reasonable request.
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Acknowledgements
This work was supported by JSPS KAKENHI Grant Numbers 18K19615, 20H03848, 22K09881, 23H03066 and 24K12848 and The Osaka Medical Research Foundation for Intractable Diseases Grant Numbers 29-1-18 and 30-2-35.
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The first and second authors equally contributed to this work. M.I., K.Ku., S.M. and T.K. designed, performed and interpreted all the experiments. K.Ku., K.Ka. and S.M. developed AAV vectors and performed experiments with the vectors. M.I., N.O., R.N. and T.O. performed mechanical stimulation experiments. K.Ka. and T.K. supervised and interpreted the data. M.I., K.Ku. and T.K. wrote the manuscript. All authors reviewed the manuscript.
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Ishii, M., Kuroda, K., Otani, N. et al. LIMK2 inactivation suppresses mechanical stimulation-induced dermal fibroblast differentiation and resistance to apoptosis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37610-y
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DOI: https://doi.org/10.1038/s41598-026-37610-y
