摘要
目的:雄激素性脱发(androgenetic alopecia,AGA)的发病机制与雄激素的水平及其代谢通路有关。雄激素受体(androgen receptor,AR)结合雄激素需要热激蛋白27(heat shock protein 27,HSP27)的协助。HSP27联合微小核糖核酸(microRNAs,miR)-1可以调控AR的表达水平。但HSP27与miR-1是否联合参与了AGA的发病目前尚不清楚。本研究通过检测男性AGA患者头皮组织中HSP27、AR及miR-1的表达水平,探讨HSP27联合miR-1的表达变化导致AR改变在AGA发病中的作用。方法:选取广州医科大学附属第一医院2019年9月—2020年2月收治的男性AGA患者46例(AGA组)以及同院同期收治的健康体检者52例(对照组)。采集其血清样本,采用酶联免疫吸附法(ELISA)检测血清二氢睾酮(dihydrotestosterone,DHT)和HSP27水平。取两组中各10例患者的头皮组织,采用蛋白质印迹法检测HSP27和AR蛋白质的表达水平,real-time PCR检测HSP27、AR和miR-1的mRNA表达水平。在人毛乳头细胞中瞬时转染HSP27 siRNA抑制HSP27的表达,同时或者分别转染miR-1及miR-1抑制剂,检测AR蛋白质表达的变化。结果:AGA组的DHT和HSP27水平均明显高于对照组[(361.4±187.7)pg/mL vs(281.8±176.6)pg/mL和(89.4±21.8)ng/mL vs(41.2±13.7)ng/mL,均P<0.05]。不同脱发程度的AGA患者血清HSP27和AR水平差异无统计学意义(P>0.05)。相关分析结果显示:AGA患者血清HSP27水平与DHT水平呈正相关(r=0.936,P<0.05),头皮组织HSP27 mRNA表达水平与miR-1 mRNA表达水平呈负相关(r=-0.640,P<0.05)。与对照组相比,AGA头皮组织中HSP27和AR蛋白质表达水平,以及HSP27 mRNA表达水平和AR mRNA表达水平均明显升高(P<0.05);而AGA患者头皮组织中miR-1表达和AR表达则明显下调(P<0.05)。体外细胞研究显示,在人毛乳头细胞中分别加入HSP27和miR-1抑制剂均能抑制AR的表达;同时抑制HSP27和miR-1的表达对AR的抑制作用具有累加效果,差异均有统计学意义(均P<0.05)。结论:HSP27和miR-1可能同时介�
Objective:The pathogenesis of androgenetic alopecia(AGA)is related to the level of androgen and its metabolic pathways.The binding of androgen and androgen receptor(AR)depends on the assistance of heat shock protein 27(HSP27).HSP27 combined with micro RNAs(miR)-1 can regulate AR levels.However,it is not clear whether HSP27 and miR-1 jointly participate in the pathogenesis of AGA.This study aims to investigate the role of AR up-regulation in the pathogenesis of AGA and underlying mechanisms.Methods:A total of 46 male AGA patients(AGA group),who admitted to the First Affiliated Hospital of Guangzhou Medical University from September 2019 to February2020,and 52 healthy controls admitted to the same period were enrolled in this study.Serum levels of dihydrotestosterone(DHT)and HSP27 in patients and healthy controls were measured by ELISA.Western blotting was used to detect the protein expression of HSP27 and AR in scalp tissues of patients and the healthy controls.The levels of HSP27,AR,and miR-1 were analyzed using real-time PCR.Human dermal papilla cells were transfected with HSP27 si RNA to inhibit the expression of HSP27.MiR-1 and miR-1 inhibitors were transfected simultaneously or separately into cells and then the changes in AR protein expression were detected.Results:The levels of DHT and HSP27 in the AGA group were(361.4±187.7)pg/mL and(89.4±21.8)ng/mL,respectively,which were higher than those in the control group[(281.8±176.6)pg/mL and(41.2±13.7)ng/mL,both P<0.05].However,there was no significant difference in serum HSP27 and AR levels among AGA patients with different degrees of hair loss(P>0.05).Correlation analysis showed that there was a positive correlation between HSP27 level and DHT level in the AGA patients(P<0.05).The level of HSP27 mRNA in scalp tissue was negatively correlated with that of miR-1 mRNA(P<0.05).Compared with the control group,the levels of HSP27 protein,AR protein,HSP27 mRNA,and AR mRNA in scalp tissues of AGA group were significantly increased(P<0.05).The up-regulation of HSP27
作者
王敏
王霞
WANG Min;WANG Xia(First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510120,China)
出处
《中南大学学报（医学版）》
CAS
CSCD
北大核心
2022年第1期72-78,共7页
Journal of Central South University ：Medical Science
