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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

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

Author(s): Shuning Ding, Yunyun Hu, Peiyu Mao, Qiu Lin and Zhitao Yao*

Volume 24, Issue 4, 2024

Published on: 12 July, 2023

Page: [516 - 523] Pages: 8

DOI: 10.2174/1566524023666230420085743

Price: $65

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Abstract

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.

Objective: To explore the specific action mechanism of estrogen treatment on IUA.

Methods: The IUA model in vivo and the isolated endometrial stromal cells (ESCs) model in vitro 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.

Results: It was found that 17β-estradiol inhibited fibrosis of ESCs by down-regulating miR-21-5p level and activating PPARα signaling. Mechanistically, miR-21-5p significantly reduced the inhibitory effect of 17β-estradiol on fibrotic ESCs (ESCs-F) and its maker protein (e.g., α-SMA, collagen I, and fibronectin), where targeting to PPARα 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 PPARα agonist caffeic acid counteracted the facilitation action of miR-21-5p on ESCs-F, which is consistent with the efficacy of estrogen intervention.

Conclusion: In brief, the above findings revealed that the miR-21-5p/PPARα 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.

Keywords: Estrogen, endometrial mechanical injury, fibrosis, fatty acid oxidation, miR-21-5p, PPARα.

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