The secretion of TGF-β3 by adipose-derived stem cells inhibits melanin synthesis and its impact on the cAMP/PKA signaling pathway.

This study aimed to investigate the role of transforming growth factor-beta 3 (TGF-β3) secreted by adipose-derived stem cells (ADSCs) in suppressing melanin synthesis during the wound healing process, particularly in burn injuries, and to explore the underlying mechanisms involving the cAMP/PKA signaling pathway. ADSCs were isolated from C57BL/6 mice and characterized using flow cytometry and differentiation assays. A burn injury model was established in mice, followed by UVB irradiation to induce hyperpigmentation. Mice were divided into four groups: control (PBS), ADSCs, ADSCs with TGF-β3 overexpression, and ADSCs with TGF-β3 knockdown. Melanin deposition was assessed via Fontana Masson staining, while ELISA measured the expression of MC1R and α-MSH. Western blotting was used to examine TGF-β3 and the activation of cAMP/PKA signaling pathway. Mice treated with ADSCs overexpressing TGF-β3 showed significant reductions in melanin deposition and suppressed expression of MC1R and α-MSH compared to controls. Western blot results revealed that the cAMP/PKA signaling pathway was downregulated in the TGF-β3-overexpressing ADSC group. In contrast, the knockdown of TGF-β3 led to increased melanin deposition and higher cAMP/PKA pathway activity, correlating with greater expression of MC1R and α-MSH. TGF-β3 secreted by ADSCs effectively inhibits melanin synthesis during wound healing, with potential effects on the cAMP/PKA signaling pathway. These findings suggest that TGF-β3 could serve as a potential therapeutic target for managing post-burn hyperpigmentation.