Quercetin regulates fibrogenic responses of endometrial stromal cell by upregulating miR-145 and inhibiting the TGF-β1/Smad2/Smad3 pathway

被引：23

作者：

Xu, Jia ^{[1
]}

Tan, Ya-Li ^{[2
]}

Liu, Qi-Ying ^{[3
]}

Huang, Zi-Chun ^{[4
]}

Qiao, Zong-Hui ^{[1
]}

Li, Tai ^{[5
]}

Hu, Zhi-Qiang ^{[5
]}

Lei, Lei ^{[2
]}

机构：

[1] Hunan Univ Tradit Chinese Med, Dept Gynaecol & Obstet, Affiliated Hosp 1, Changsha 410007, Peoples R China

[2] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China

[3] Changsha Maternal & Child Hlth Hosp, Dept Gynaecol & Obstet, Changsha 410000, Peoples R China

[4] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Dept Gynaecol, Changsha 410005, Peoples R China

[5] Hunan Univ Chinese Med, Sch Clin Med, Changsha 410208, Peoples R China

来源：

ACTA HISTOCHEMICA | 2020年 / 122卷 / 07期

关键词：

Endometrial fibrosis; microRNA-145; quercetin; TGF-beta; 1; TGFBR2; CANCER PREVENTION; SIGNALING PATHWAY; FIBROSIS; PROLIFERATION; INVASION; TGFBR2; TISSUE;

D O I：

10.1016/j.acthis.2020.151600

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Objectives: Aim of this study is to explore whether quercetin can inhibit the enlarged fibrogenic responses of endometrial stromal cells by increasing the level of microRNA-145 (miR-145) and mediating the TGF-beta 1/Smad2/Smad3 signaling pathway, and to discuss the mechanism of signal transduction, further to provide experimental basis for revealing the pathophysiological mechanism and seeking new strategies for effective prevention and treatment of endometrial fibrosis. Methods: The expression levels of miR-145 and TGF-beta receptor 2 (TGFBR2) were detected by RT-qPCR analysis. Expressions of alpha-smooth muscle actin (alpha-SMA) and vimentin were examined by immunofluorescence staining. Cell viability was measured by MIT assay. The protein expression of collagen type 1 alpha 1 (Coll al), alpha-SMA, fibronectin (FN), TGFBR2, transforming growth factor (TGF-beta 1), Smad2/3, phospho-Smad2/3 (p-Smad2/3) were detected by western blot analysis. The interaction between miR-145 and TGFBR2 was confirmed by dual-luciferase reporter gene assay. Results: The expression level of miR-145 was decreased, whereas TGFBR2 was increased in intrauterine adhesion tissue. The expression levels of COL1A1, alpha-SMA, FN, TGFBR2, and p-Smad2/3 were increased, whereas miR-145 and cell proliferation were decreased in human endometrial stromal cells (hESCs) in response to TGF-beta 1 stimulation in a time and dose-dependent manner, which could be reversed by quercetin. Furthermore, quercetin regulates cell fibrogenic responses of endometrial stromal cells via miR-145/TGF-beta 1/Smad2/Smad3 pathway. Conclusions: These findings indicated that quercetin have a significant anti-fibrotic effect and could upregulate miR-145 and inhibit activation of TGF-beta 1/Smad2/Smad3 pathway to regulate TGF-beta 1 induced fibrogenic responses of endometrial stromal cells, which may serve as a potential therapeutic agent for endometrial fibrosis.

引用

页数：9

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