miR-93介导转化生长因子-β1调节Ⅲ型胶原蛋白在压力性尿失禁中的意义

Significance of miR-93-mediated TGF-β1 regulation of type Ⅲ collagen in stress urinary incontinence

目的探讨微RNA-93(miR-93)介导转化生长因子-β1(TGF-β1)调节Ⅲ型胶原蛋白在压力型尿失禁(SUI)中的表达意义。方法2014年1月至2018年1月,选取无锡市妇幼保健院收治的SUI病人(SUI组53例)以及同期行妇科良性肿瘤治疗且术前检查无SUI及其他盆腔器官脱垂临床症状的病人(无SUI组53例)为研究对象。取受试者阴道壁组织,以RT-PCR测定miR-93的表达,以蛋白印迹法测定TGF-β1及Ⅲ型胶原蛋白的表达,结合荧光素酶报告分析测定miR-93与TGF-β1的相关性。结果miR-93在SUI病人阴道壁组织中的表达低于无SUI组(0.63±0.18)比(1.12±0.23),TFG-β1及CollagenⅢ在SUI病人阴道壁组织中的表达亦低于无SUI组[TFG-β1(0.49±0.12)比(0.67±0.15),CollagenⅢ(0.22±0.05)比(0.31±0.09)]。SUI组与无SUI组相比,miR-93表达降低[(0.26±0.04)比(1.05±0.12)],TFG-β1及CollagenⅢ在SUI原代成纤维细胞中的表达均降低[TFG-β1(0.92±0.20)比(1.15±0.07);CollagenⅢ(0.32±0.05)比(1.02±0.13)]。miR-93基因可与TFG-β1基因结合,并且通过结合提高了TFG-β1的表达。进一步研究证实miR-93过表达的情况下可以提高TFG-β1的表达,而当miR-93的表达被抑制时,TFG-β1的表达亦下调(t=6.590;P=0.007)。结论SUI病人中,miR-93表达降低,介导TGF-β1表达下调,最终导致胶原Ⅲ含量降低。

Objective nary incontinence.Methods From January 2014 to January 2018,patients with stress-type urinary incontinence(observation group n=53)and gynecological benign tumor patients(n=53 of control group)admitted to Wuxi Maternal and Child Health Care Hospital affiliated to Nanjing Medical University were enrolled in the study.The vaginal wall tissue of the subjects was taken and the expression of miR-93 was determined by RT-PCR.The expressions of TGF-β1 and typeⅢcollagen were determined by Western Blot method,and the correlation between miR-93 and TGF-β1 was detected by luciferase reporter assay.Results The expression of miR-93 in the vaginal wall of Sui patients was lower than that of the control group(0.630±0.18 vs.1.12±0.23),and the expressions of TFG-βand collagenⅢin vaginal wall of Sui patients were also lower than those of the control group[TFG-β1(0.49±0.12)vs.(0.67±0.15);CollagenⅢ(0.22±0.05)vs.(0.31±0.09)].Compared with the control group,the expression of mir-93 in Sui group was decreased(0.262±0.04 vs.1.05±0.12),the expression of TFG-βand collagenⅢin Sui fibroblasts decreased[TFG-β1(0.92±0.20)vs.(1.15±0.07)and Collagen II(0.32±0.05)vs.(1.02±0.13)].MiR-93 can bind to TFG-β1 gene,and the expression of TFG-β1 is enhanced by the binding.In this study,the effects of mir-93 overexpression and inhibition on TFG were further determined by Western blot,further confirming that miR-93 overexpression can improve TFG-β.When the expression of mir-93 was inhibited,TFG-βdecreased(t=6.590;P=0.007).Conclusion sIn patients with stress urinary incontinence,the expression of miR-93 is decreased,which mediates the down-regulation of TGF-β1 expression,which ultimately leads to a decrease in collagenⅢcontent.