Abstract

Hypertrophic scar (HS) is a dermatosis hallmarked by fibrosis in skin fibroblasts. Histone deacetylase 6 (HDAC6) is involved in the process of human fibrotic diseases, but the action of HDAC6 in skin fibrosis remains unclear. Herein, we explored the effect of tubacin (a selective inhibitor for HDAC6) on the fibrosis of human dermal fibroblasts (HDFs). Transforming growth factor β1 (TGF-β1)-induced HDFs were used as a cell model in vitro. The viability, proliferation, and migration of HDFs were detected by cell counting, 5-ethynyl-2'-deoxyuridine, and transwell assays. The myofibroblast differentiation of HDFs was determined by detecting alpha-SMA (α-SMA) expression by immunofluorescence staining. The fibrosis of HDFs was determined by measurement of type I collagen (COL1) and fibronectin (FN) protein levels. Relative protein levels of COL1, FN, HDAC6, p-Smad3, acetylated α-tubulin, and acetylated Hsp90 were evaluated by western blot or immunoprecipitation. Relative mRNA levels of HDAC6 were detected by quantitative polymerase chain reaction. TGF-β1-induced proliferation and migration of HDFs accompanied by elevated α-SMA, COL1, and FN expression levels, but tubacin treatment undermined the above changes in a concentration-dependent manner, manifesting that tubacin lessened urged HDF proliferation, myofibroblast differentiation, migration, and ECM deposition. Importantly, TGF-β1 elevated HDAC6 and p-Smad3 protein levels and decreased acetyl-α-tubulin/Hsp90 in HDFs, yet these changes were partly reversed by tubacin treatment. Tubacin mitigated TGF-β1-induced HDF proliferation, myofibroblast differentiation, migration, and ECM deposition via inhibiting HDAC6-mediated deacetylation of α-tubulin and Hsp90, providing important theoretical evidence for tubacin as a potential strategy for the treatment of HS and skin fibrosis.