Hye-Rim Moon1, Joon Min Jung2, Su Yeon Kim2, Youngsup Song3, Sung Eun Chang4. 1. Beautiful skin clinic, 16-26, Sanbon-ro 323beon-gil, Gunpo-si, Gyeonggi-do, Republic of Korea. 2. Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 3. Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: ysong@amc.seoul.kr. 4. Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: changse2016@gmail.com.
Abstract
BACKGROUND: Ultraviolet radiation (UVR) is the most well-known cause of skin pigmentation accompanied with photoaging. Transforming growth factor (TGF)-β1 was previously shown to have anti-melanogenic property; however, it can induce scarring in skin. OBJECTIVE: We investigated the effect of TGF-β3 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-β3. RESULTS: While UVB irradiation or SCF/ET-1 enhanced melanogenesis, TGF-β3 effectively inhibited melanin accumulation and tyrosinase activity via downregulation of the extracellular signal-regulated kinase (ERK)/microphthalmia-associated transcription factor (MITF) pathway. TGF-β3 increased the expression of differentiation markers of keratinocytes. CONCLUSION: TGF-β3 effectively suppressed UVR-stimulated melanogenesis indicating that topical TGF-β3 may be a suitable candidate for the treatment of UV-associated hyperpigmentation disorders.
BACKGROUND: Ultraviolet radiation (UVR) is the most well-known cause of skin pigmentation accompanied with photoaging. Transforming growth factor (TGF)-β1 was previously shown to have anti-melanogenic property; however, it can induce scarring in skin. OBJECTIVE: We investigated the effect of TGF-β3 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-β3. RESULTS: While UVB irradiation or SCF/ET-1 enhanced melanogenesis, TGF-β3 effectively inhibited melanin accumulation and tyrosinase activity via downregulation of the extracellular signal-regulated kinase (ERK)/microphthalmia-associated transcription factor (MITF) pathway. TGF-β3 increased the expression of differentiation markers of keratinocytes. CONCLUSION: TGF-β3 effectively suppressed UVR-stimulated melanogenesis indicating that topical TGF-β3 may be a suitable candidate for the treatment of UV-associated hyperpigmentation disorders.