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Quercetin promotes human epidermal stem cell proliferation through the estrogen receptor/β-catenin/c-Myc/cyclin A2 signaling pathway

查看全文 作　　者：Zhaodong [1]Wang;Guangliang [2]Zhang;Yingying [4]Le;Jihui [2]Ju;Ping [1]Zhang;Dapeng [1]Wan;Qiang [2]Zhao;Guangzhe [2]Jin;Hao [1]Su;Jinwei [1]Liu;Jiaxuan [1]Feng;Yi [3]Fu;Ruixing [1,2]Hou 高影响力作者 机构地区：[1]Institute of Hand Surgery,Ruihua Affiliated Hospital of Soochow University,Suzhou 215104,China;[2]Department of Hand Surgery,Ruihua Affiliated Hospital of Soochow University,Suzhou 215104,China;[3]Department of Human Anatomy,Histology and Embryology,School of Biology and Basic Medical Sciences,Soochow University,Suzhou 215123,China;[4]CAS Key Laboratory of Nutrition,Metabolism and Food Safety,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China高影响力机构 出　　处：《Acta Biochimica et Biophysica Sinica》索引2020年第52卷第10期,共9页高影响力期刊 基　　金：This work was supported by the grants from the National Natural Science Foundation of China(No.31900969);the Suzhou Municipal Science and Technology Bureau(Nos.SYSD2017049 and SYS2018002);the Gusu Health Talent Training Project of Suzhou(No.GSW S2019088). 摘　　要：Skin epidermal stem cells(EpSCs)play an important role in wound healing.Quercetin is a phytoestrogen reported to accelerate skin wound healing,but its effect on EpSCs is unknown.In this study,we investigated the effect of quercetin on human EpSC proliferation and explored the underlying mechanisms.We found that quercetin at 0.1~1μM significantly promoted EpSC proliferation and increased the number of cells in S phase.The pro-proliferative effect of quercetin on EpSCs was confirmed in cultured human skin tissue.Mechanistic studies showed that quercetin significantly upregulated the expressions ofβ-catenin,c-Myc,and cyclins A2 and E1.Inhibitor forβ-catenin or c-Myc significantly inhibited quercetin-induced EpSC proliferation.Theβ-catenin inhibitor XAV-939 suppressed quercetin-induced expressions ofβ-catenin,c-Myc,and cyclins A2 and E1.The c-Myc inhibitor 10058-F4 inhibited the upregulation of c-Myc and cyclin A2 by quercetin.Pretreatment of EpSCs with estrogen receptor(ER)antagonist ICI182780,but not the G protein-coupled ER1 antagonist G15,reversed quercetin-induced cell proliferation and upregulation ofβ-catenin,c-Myc,and cyclin A2.Collectively,these results indicate that quercetin promotes EpSC proliferation through ER-mediated activation ofβ-catenin/c-Myc/cyclinA2 signaling pathway and ER-independent upregulation of cyclin E1 and that quercetin may accelerate skin wound healing through promoting EpSC proliferation.As EpSCs are used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering,quercetin is a useful reagent to expand EpSCs for basic research,skin wound treatment,and skin tissue engineering. 关 键 词：QUERCETIN epidermal stem cell cell proliferation estrogen receptor Β-CATENIN
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