Zhouwei Wu1, Hiroshi Uchi2, Saori Morino-Koga3, Weimin Shi4, Masutaka Furue5. 1. Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China; Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan. Electronic address: uchihir@dermatol.med.kyushu-u.ac.jp. 3. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 4. Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China. 5. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan.
Abstract
BACKGROUND: Aquaporin 3 (AQP3) is the predominant aquaporin in the skin and is overexpressed in hyperplastic epidermal disorders. Upregulation of AQP3 contributes to keratinocyte proliferation and epidermal hyperplasia. Resveratrol, a natural polyphenol, has an anti-proliferative effect on normal human epidermal keratinocytes (NHEKs), but its exact mechanism remains largely unknown. OBJECTIVE: To investigate the ability and mechanism of resveratrol to affect the proliferation and the AQP3 expression in NHEKs. METHODS: NHEKs treated with resveratrol were analyzed. BrdU incorporation assay, real-time PCR, Western blotting and RNA interference using small interfering RNA were employed. RESULTS: At non-toxic concentrations (less than 40μM), resveratrol inhibited the proliferation of NHEKs. Resveratrol inhibited the ERK phosphorylation and the AQP3 expression with reciprocal upregulation of ARNT expression in a concentration-dependent manner. The inhibitory effects of resveratrol on the ERK phosphorylation and the AQP3 expression were canceled by transfection of siRNA for ARNT, but not by that for AhR. Furthermore, the induction effect of resveratrol on ARNT expression was canceled after SIRT1 was knocked down in NHEKs. CONCLUSION: Resveratrol inhibited NHEK proliferation by downregulating the expression of AQP3 in an SIRT1/ARNT/ERK dependent fashion. This novel mechanism may facilitate drug innovation for hyperplastic skin disorders.
BACKGROUND:Aquaporin 3 (AQP3) is the predominant aquaporin in the skin and is overexpressed in hyperplastic epidermal disorders. Upregulation of AQP3 contributes to keratinocyte proliferation and epidermal hyperplasia. Resveratrol, a natural polyphenol, has an anti-proliferative effect on normal human epidermal keratinocytes (NHEKs), but its exact mechanism remains largely unknown. OBJECTIVE: To investigate the ability and mechanism of resveratrol to affect the proliferation and the AQP3 expression in NHEKs. METHODS: NHEKs treated with resveratrol were analyzed. BrdU incorporation assay, real-time PCR, Western blotting and RNA interference using small interfering RNA were employed. RESULTS: At non-toxic concentrations (less than 40μM), resveratrol inhibited the proliferation of NHEKs. Resveratrol inhibited the ERK phosphorylation and the AQP3 expression with reciprocal upregulation of ARNT expression in a concentration-dependent manner. The inhibitory effects of resveratrol on the ERK phosphorylation and the AQP3 expression were canceled by transfection of siRNA for ARNT, but not by that for AhR. Furthermore, the induction effect of resveratrol on ARNT expression was canceled after SIRT1 was knocked down in NHEKs. CONCLUSION:Resveratrol inhibited NHEK proliferation by downregulating the expression of AQP3 in an SIRT1/ARNT/ERK dependent fashion. This novel mechanism may facilitate drug innovation for hyperplastic skin disorders.
Authors: Claudinéia Pereira Maranduba; Gustavo Torres Souza; Antônio Márcio Resende do Carmo; José Marcelo Sallabert de Campos; Nádia Rezende Barbosa Raposo; Marcelo de Olivera Santos; Carlos Magno da Costa Maranduba; Fernando de Sá Silva Journal: Childs Nerv Syst Date: 2020-11-20 Impact factor: 1.475