The effects of Tubacin, a HDAC6 inhibitor on skin wound healing and its mechanism

Abstract

Background Wound healing is a common clinical pathological process that is interrupted when abnormal pathological factors are present, which can significantly delay wound healing and lead to complication. Epigenetic modification plays an important role in wound repair, including histone deacetylase HDAC6-mediated regulation of cell morphology, autophagy, migration, inflammation, and oxidative stress.Therefore, this study aimed to investigate how HDAC6 inhibitors affect the proliferation and migration of dermal fibroblasts in allogeneic skin wound repair. Methods and results We effectively isolated primary skin fibroblasts from newborn rat skin tissue, and the effects of TGFB1 and different concentrations of HDAC6 inhibitor Tubacin on skin fibroblast growth and migration were detected using the MTT assay and scratch test. Tubacin was discovered to decrease fibroblast growth and migration. Tubacin down-regulated the expression levels of COL3, p-AKT, HDAC6, Col1a1, -SMA, and p-ERK, which were up-regulated by TGF-1, in fibroblasts treated with TGF-1 and different doses of Tubacin. Tubacin also increased the protein levels of ace–tubulin and CD31 (platelet endothelial cell adhesion molecule). To examine the impact of the HDAC6 inhibitor Tubacin in skin wound regeneration, we created a full-thickness wound model on the back of rats and used Western blot to assess the expression levels of HDAC6, acetylated -tubulin, COL1A1, COL3, and -SMA. The results demonstrated that trauma increased the expression levels of HDAC6 and acetylated -tubulin in the skin; these findings suggest that HDAC6 and acetylated -tubulin may be involved in wound repair. Tubacin, on the other hand, decreased the protein levels of HDAC6 and acetylated-tubulin, as well as the protein levels of COL1A1 and COL3. The mechanism could be that COL1A1, COL3, and -SMA expression, which are involved in pathological wound repair, are blocked via modulating the TGF-β-PI3K-Akt pathway and MAPK/ERK signaling.Thus, our results implies that inhibiting HDAC6 plays a beneficial function in wound healing and scar formation. Conclusion Tubacin inhibits fibroblast proliferation and migration, as well as the expression of COL1A1, COL3, and -SMA, all of which are involved in pathological wound repair. It also promotes the expression of CD31, which is associated with inflammation or angiogenesis, by regulating the tgf-PI3K-Akt pathway and the MAPK/ERK signaling pathway.