Nrf2信号通路调控自噬对UVA诱导人真皮成纤维细胞凋亡的作用  

Effect of Nrf2 Signaling Pathway-Induced Autophagy in Human Fibroblasts Apoptosis Under UVA Irradiation

作　　者：毛汉潇 刘汝兰 谭自敏 谭小琦 熊霞 何渊民 MAO Hanxiao;LIU Rulan;TAN Zimin;TAN Xiaoqi;XIONG Xia;HE Yuanmin(Department of Dermatology,Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属医院皮肤科,四川泸州646000

出　　处：《中国皮肤性病学杂志》2023年第5期524-529,共6页The Chinese Journal of Dermatovenereology

基　　金：四川省应用基础研究项目(2018JY0406)。

摘　　要：目的探讨Nrf2信号通路介导的细胞自噬在UVA诱导人皮肤成纤维细胞凋亡过程中的作用。方法体外培养正常人皮肤成纤维细胞,分为对照组、UVA组、自噬诱导剂雷帕霉素(rapamycin,RAPA)组、自噬抑制3-甲基嘌呤(3-methyladenine,3-MA)组、核因子E2相关因子2(Nrf2)抑制剂(ML385)组及干涉(siRNA)组;各实验组经8 J/cm^(2)的UVA照射;采用流式细胞术检测成纤维细胞凋亡;CCK-8检测细胞活性变化;Western blot检测细胞自噬及凋亡关键分子、p62及Nrf2蛋白表达水平。结果经8 J/cm^(2)的UVA照射后成纤维细胞凋亡比例增加、胞内自噬水平显著升高;自噬抑制剂3-MA处理后可显著促进UVA照射引起的成纤维细胞凋亡;而自噬促进剂RAPA处理细胞后,细胞凋亡率较UVA组相比显著降低(P<0.01);与对照组相比,UVA照射后胞核Nrf2表达显著增高;ML385阻断Nrf2入核及使用siRNA干涉Nrf2表达后,自噬关键蛋白LC3Ⅱ/Ⅰ降低(P<0.01),p62表达显著减少(P<0.01),凋亡相关蛋白Cleaved Caspase3表达增加(P<0.01)。结论UVA照射可通过Nrf2及下游p62信号通路上调细胞自噬水平,抑制UVA诱导成纤维细胞凋亡。Objective To investigate the effect of Nrf2 signaling-induced autophagy in UVA-induced human fibroblasts apoptosis.Methods Human skin fibroblasts were divided into the following groups:control,UVA,RAPA,3-MA,ML385 and Nrf2-siRNA group.All these groups were irradiated with 8 J/cm^(2)UVA.Cell apoptosis was detected by flow cytometry;CCK-8 assay was used to detect cell viability;Cell autophagy-associated key protein(p62 and Nrf2)were detected by Western blot assay.Results UVA irradiation increased fibroblasts apoptosis and cell autophagy.The inhibition of cell autophagy enhanced fibroblasts apoptosis after UVA irradiation;After treatment with RAPA,the apoptosis rate was significantly lower than that in the UVA group(P<0.01).In addition,UVA irradiation increased Nrf2 expressionin nucleus.ML385 and Nrf2-siRNA treatment significantly decreased LC3Ⅱ/Ⅰand p62 expression(P<0.01),but increased Cleaved Caspase3 expression(P<0.01).Conclusion UVA irradiation can enhance cell autophagy by activating Nrf2 signaling,thereby reducing UVA-induced fibroblasts apoptosis.

关 键 词：UVA 成纤维细胞 细胞自噬 细胞凋亡 

分 类 号：R758.1[医药卫生—皮肤病学与性病学]