PVT1通过TGF-β1/SMAD通路促进子宫内膜基质细胞过度纤维化的研究  

Study on plasmacytoma variant translocation gene 1 via transforming growth factor-β1/SMAD pathway promoting excessive fibrosis of endometrial stromal cells

作　　者：杨强 张志伟 邱娟娟 王雨潇 YANG Qiang;ZHANG Zhiwei;QIU Juanjuan;WANG Yuxiao(Department of Obstetrics and Gynecology,the First Affiliated Hospital of Shandong First Medical University,Jinan 250014,Shandong,China;Department of Obstetrics,the First Affiliated Hospital of Shandong First Medical University,Jinan 250014,Shandong,China)

机构地区：[1]山东第一医科大学第一附属医院妇产科,济南250014 [2]山东第一医科大学第一附属医院产科,济南250014

出　　处：《中国性科学》2024年第1期82-86,共5页Chinese Journal of Human Sexuality

基　　金：山东省科技厅重点研发计划(2017G006023)。

摘　　要：目的探讨长链非编码RNA(lncRNA)浆细胞瘤多样异位基因1(PVT1)在调控子宫内膜基质细胞纤维化中的病理生理作用及分子机理。方法通过实时荧光定量聚合酶链反应(qRT-PCR)检测人子宫内膜基质细胞(HESCs)中PVT1、胶原蛋白Ⅰ、胶原蛋白Ⅲ、转化生长因子-β1(TGF-β1)、SMAD2及SMAD3的表达水平。结果PVT1过表达促进HESCs增殖(P<0.05),而PVT1沉默抑制HESCs增殖(P<0.05)。过表达PVT1在HESCs中上调胶原蛋白Ⅰ和胶原蛋白ⅢmRNA的表达(P<0.05),而PVT1被敲除时,胶原蛋白Ⅰ和胶原蛋白ⅢmRNA的表达水平被显著下调(P<0.05)。过表达PVT1在HESCs中可以进一步上调TGF-β1/SMAD信号相关基因(TGF-β1、SMAD2、SMAD3)的表达(P<0.05)。当PVT1被敲除时,TGF-β1/SMAD信号相关基因胶原蛋白Ⅰ和胶原蛋白ⅢmRNA的表达水平被显著下调(P<0.05)。PVT1可诱导HESCs上清液中TGF-β1的产生(P<0.05)。结论PVT1可通过TGF-β1/SMAD通路促进子宫内膜基质细胞过度纤维化而产生胶原蛋白。同时,PVT1可能是一个用于治疗子宫内膜粘连的新靶点。Objective To explore the pathophysiological role and molecular mechanism of long noncoding RNA(lncRNA)plasmacytoma variant translocation gene 1(PVT1)in regulating endometrial stromal cells fibrosis.Methods The expression levels of PVT1,collagenⅠ,collagenⅢ,transforming growth factorβ1(TGF-β1),SMAD2 and SMAD3 in human endometrial stromal cells(HESCs)were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Results Overexpression of PVT1 promoted proliferation of HESCs(P<0.05),while PVT1 silencing inhibited proliferation of HESCs(P<0.05).Overexpression of PVT1 up-regulated mRNA expression of collagenⅠand collagenⅢin HESCs(P<0.05),whereas the mRNA expression levels of collagenⅠand collagenⅢwere significantly down-regulated when PVT1 was knocked down(P<0.05).Overexpression of PVT1 in HESCs could further upregulate the expression of TGF-β1/SMAD signal-related genes(TGF-β1,SMAD2,SMAD3)(P<0.05).When PVT1 was knocked down,the expression levels of mRNA of TGF-β1/SMAD signal-related genes collagenⅠand collagenⅢwere significantly down-regulated(P<0.05).PVT1 could induce the production of TGF-β1 in the supernatant of HESCs(P<0.05).Conclusions PVT1 may promote excessive fibrosis of endometrial stromal cells and produce collagen through the TGF-β1/SMAD pathway.Meanwhile,PVT1 may be a novel target for the treatment of endometrial adhesions.

关 键 词：长链非编码RNA 浆细胞瘤多样异位基因1 纤维化 子宫内膜基质细胞 转化生长因子-β1/SMAD通路 

分 类 号：R711[医药卫生—妇产科学]