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Study on the Mechanism of Estrogen Regulating Endometrial Fibrosis After Mechanical Injury Via MIR-21-5P/PPARΑ/FAO Axis

[ Vol. 24 , Issue. 4 ]


Shuning Ding, Yunyun Hu, Peiyu Mao, Qiu Lin and Zhitao Yao*   Pages 516 - 523 ( 8 )


<p> Background: Intrauterine adhesion (IUA) caused by endometrial mechanical injury has been found as a substantial risk factor for female infertility (e.g., induced abortion). Estrogen is a classic drug for the repair of endometrial injury, but its action mechanism in the clinical application of endometrial fibrosis is still unclear. <p> Objective: To explore the specific action mechanism of estrogen treatment on IUA. <p> Methods: The IUA model <i>in vivo</i> and the isolated endometrial stromal cells (ESCs) model <i>in vitro</i> were built. Then CCK8 assay, Real-Time PCR, Western Blot and Dual- Luciferase Reporter Gene assay were applied to determine the targeting action of estrogen on ESCs. <p> Results: It was found that 17β-estradiol inhibited fibrosis of ESCs by down-regulating miR-21-5p level and activating PPAR&#945; signaling. Mechanistically, miR-21-5p significantly reduced the inhibitory effect of 17&#946;-estradiol on fibrotic ESCs (ESCs-F) and its maker protein (e.g., &#945;-SMA, collagen I, and fibronectin), where targeting to PPAR&#945; 3’- UTR and blocked its activation and transcription, thus lowering expressions of fatty acid oxidation (FAO) associated key enzyme, provoking fatty accumulation and reactive oxygen species (ROS) production, resulting in endometrial fibrosis. Nevertheless, the PPAR&#945; agonist caffeic acid counteracted the facilitation action of miR-21-5p on ESCs-F, which is consistent with the efficacy of estrogen intervention. <p> Conclusion: In brief, the above findings revealed that the miR-21-5p/PPAR&#945; signal axis played an important role in the fibrosis of endometrial mechanical injury and suggested that estrogen might be a promising agent for its progression.</p>


Estrogen, endometrial mechanical injury, fibrosis, fatty acid oxidation, miR-21-5p, PPAR&#945;.


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