title: MicroRNA-29b Inhibits Endometrial Fibrosis by Regulating the Sp1-TGF-β1/Smad-CTGF Axis in a Rat Model.
abstract: Intrauterine adhesions (IUAs), which are characterized by endometrial fibrosis, increase the risk of secondary infertility and recurrent miscarriage. MicroRNA-29 (miR-29) is a potent inhibitor of TGF-β1/Smad signaling. In this study, we investigated the therapeutic potential of agomir-29b, an miR-29b mimic, in endometrial fibrosis induced by dual injury (uterine curettage and lipopolysaccharide treatment) in a rat model of IUA and explored the underlying mechanism. We found that injured rats developed endometrial fibrosis characterized by increased COL1A1 and α-smooth muscle actin expression and decreased E-cadherin expression, associated with a loss of miR-29b. Overexpression of miR-29b before injury prevented endometrial fibrosis including collagen accumulation and epithelial-mesenchymal transition. Delay of agomir-29b treatment until endometrial fibrosis was established on day 4 also halted the progression of disease. Further experiments indicated that miR-29b inhibited endometrial fibrosis via blockade of the Sp1-TGF-β1/Smad-CTGF pathway. In conclusion, agomir-29b may act as a novel and effective therapeutic agent against IUAs.
authors.affiliation: Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China Currently affiliated with the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Jingxiong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Bohong
authors.initials: B
authors.lastname: Cen
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China heyuanli310@126.com.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: He
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor / Q000502:physiology*; D004195:Disease Models, Animal; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051785:Smad Proteins / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: C526316:CCN2 protein, rat; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D051785:Smad Proteins; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor
keywords: TGF-β signaling; agomir-29b; endometrial fibrosis; epithelial–mesenchymal transition; intrauterine adhesions