GATA3 ameliorates melanocyte injuries in vitiligo through SIRT3-mediated HMGB1 deacetylation

Vitiligo is a skin depigmentation disorder. GATA3 expression is downregulated in vitiligo patients, and its role and regulatory mechanism in vitiligo are unclear. GATA3 and HMGB1 levels were detected by qRT-PCR in peripheral blood cells of vitiligo patients and healthy controls, as well as H₂ O₂ -treated PIG1 cells. Their expression correlation was assessed by Pearson analysis. qRT-PCR, MTT assay, Ki67 immunostaining, flow cytometry, ELISA and Western blot were applied to determine GATA3 expression, cell survival, cell proliferation, cell apoptosis, melanin contents, and melanin-related protein expressions. The cellular distributions of HMGB1 and its deacetylation levels were detected by Western blot. The binding of GATA3 to SIRT3 promoter and effects on SIRT3 expression and HMGB1 deacetylation was determined by dual-luciferase assay, ChIP assay, and Western blot. GATA3 was decreased, and HMGB1 was increased in vitiligo. Pearson correlation assay showed that they were negatively correlated. H₂ O₂ significantly inhibited cell survival, proliferation, melanin secretion, and melanin-related protein expressions but remarkably increased cell apoptosis. GATA3 overexpression could distinctly reverse the effects of H₂ O₂ through decreasing HMGB1 expression and retained HMGB1 in nuclear due to the decreased HMGB1 acetylation. GATA3 bound to the SIRT3 and subsequently decreased H₂ O₂ -induced HMGB1 acetylation. Overexpressing HMGB1 or knockdown of SIRT3 could reverse the effects of GATA3 overexpression. GATA3 inhibited H₂ O₂ -induced injury in PIG1 cells and enhanced melanin secretion by SIRT3-regulated HMGB1 deacetylation, which might provide new evidence to treat vitiligo.