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MicroRNA-29b Inhibits Endometrial Fibrosis by Regulating the Sp1-TGF-β1/Smad-CTGF Axis in a Rat Model

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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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, No. 253 Gongye Road, Guangzhou, 510282, China

    Jingxiong Li PhD & Yuanli He MD

  2. Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

    Shaohua Du MD

  3. Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

    Xiujie Sheng MD & Juan Liu MD

  4. Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Bohong Cen MD

  5. Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Feng Huang MD

  6. Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

    Jingxiong Li PhD

Authors
  1. Jingxiong Li PhD
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  2. Shaohua Du MD
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  3. Xiujie Sheng MD
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  4. Juan Liu MD
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  5. Bohong Cen MD
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  6. Feng Huang MD
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  7. Yuanli He MD
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Correspondence to Yuanli He MD.

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Li, J., Du, S., Sheng, X. et al. MicroRNA-29b Inhibits Endometrial Fibrosis by Regulating the Sp1-TGF-β1/Smad-CTGF Axis in a Rat Model. Reprod. Sci. 23, 386–394 (2016). https://doi.org/10.1177/1933719115602768

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  • DOI: https://doi.org/10.1177/1933719115602768

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