TGF-β3 suppresses melanogenesis in human melanocytes cocultured with UV-irradiated neighboring cells and human skin

Background: Ultraviolet radiation (UVR) is the most well-known cause of skin pigmentation accompanied with photoaging. Transforming growth factor (TGF)-beta 1 was previously shown to have anti-melanogenic property; however, it can induce scarring in skin. Objective: We investigated the effect of TGF-beta 3 on melanogenesis in human melanocytes cocultured with UV-irradiated skin constituent cells, and UV-irradiated human skin. Methods: UVB irradiation or treatment with stem cell factor (SCF) and endothelin-1 (ET-1) was applied to human melanocytes cocultured with keratinocytes and/or fibroblasts and ex vivo human skin. Mechanistic pathways were further explored after treatment with TGF-beta 3. Results: While UVB irradiation or SCF/ET-1 enhanced melanogenesis, TGF-beta 3 effectively inhibited melanin accumulation and tyrosinase activity via downregulation of the extracellular signal-regulated kinase (ERK)/microphthalmia-associated transcription factor (MITF) pathway. TGF-beta 3 increased the expression of differentiation markers of keratinocytes. Conclusion: TGF-beta 3 effectively suppressed UVR-stimulated melanogenesis indicating that topical TGF-beta 3 may be a suitable candidate for the treatment of UV-associated hyperpigmentation disorders. (C) 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.