TGF-β3의 멜라닌 생성 억제 효과와 각질형성세포와 섬유아세포의 기능에 미치는 영향에 대한 연구

Abstract

Background and Objectives: Transforming growth factor-β (TGF-β) is multifunctional growth factor with important roles in cell development, differentiation, and apoptosis. The role of TGF-β1 in melanogenesis has been already studied but functional property of TGF-β3 in melanogenesis and other effects on keratinocytes (KC) and fibroblasts (FB) are not fully understood. The present study aims to investigate the effect of TGF- β3 on melanogenesis in melanocytes (MC). In addition, we investigated the influence of TGF-β3 in differentiation of KC and cellular senescence of ultraviolet (UV)-damaged FB. Materials and methods: Stimulated co-culture of normal human melanocytes (NHM) and KC or FB as well as B16F10 and Mel-Ab cell monoculture, anti-melanogenic property of TGF- β3 was investigated. In UV-treated KC and FB, expression change of proteins related to differentiation and senescence by treatment of TGF- β3 was determined. Results: TGF- β3 inhibited melanin production and decreased tyrosinase activity in monoculture of mouse cells. As to co-culture of human melanocytes, in stem cell factor (SCF)/endothelin-1 (ET-1) stimulated NHM/KC or in UV stimulated NHM/FB, TGF-β3 effectively inhibited melanogenesis. We then assessed the impact of TGF-β3 on KC and FB. TGF- β3 increased the expression of involucrin, filaggrin, p21 and thymic stromal lymphopoietin (TSLP) in KC. In addition, the UVB-induced p53 expression was downregulated by TGF- β3 treatment in UVB-irradiated FB. As Smad pathways are known to be important players in TGF-β signaling, when we checked, TGF-β3 induced the expression of phosphorylated Smad 2 and 3 in both KC and FB. Conclusion: Altogether, our findings suggest that TGF-β3 suppress melanogenesis while improving function of KC and photodamaged FB. Topical TGF-β3 may be useful for photoaging associated hyperpigmentation disorders.