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image of Adiponectin Ameliorates Intrauterine Adhesion-Related Endometrial Inflammation and Fibrotic Changes by Downregulating the NLRP3/IL-1β/TGF-β1 Axis

Abstract

Introduction

Intrauterine Adhesions (IUA), a common gynecological condition often caused by infection or endometrial injury, significantly impact women's reproductive and mental health. Its unclear pathogenesis hinders the development of effective treatments. Adiponectin, a bioactive protein with anti-inflammatory and anti-fibrotic properties, may offer therapeutic potential. This study investigates adiponectin's effects and mechanisms in IUA to inform new clinical strategies..

Methods

Endometrial tissues from IUA patients and controls were analyzed immunohistochemistry to assess NLRP3, IL-1β, TGF-β1, and adiponectin expression. A human IUA cell model was established by stimulating human endometrial stromal cells (HESCs) with TGF-β1 (10 ng/ml, 48 hours). Interventions using the NLRP3 inhibitor MCC950, activator nigericin sodium salt, and adiponectin were applied. Protein and mRNA expression levels of NLRP3, IL-1β, TGF-β1, α-SMA, and COL1A1 were evaluated Western blot and RT-qPCR. , IUA model rats were treated with adiponectin, and uterine morphology, gland count, collagen deposition, and inflammatory/fibrotic markers were analyzed.

Results

NLRP3, IL-1β, and TGF-β1 expression were significantly upregulated in IUA patient tissues, while adiponectin was downregulated (<0.05). In the TGF-β1-induced IUA cell model, NLRP3 inhibition with MCC950 reduced IL-1β and TGF-β1 levels, whereas NLRP3 activation with nigericin increased them. Adiponectin intervention significantly decreased NLRP3, IL-1β, TGF-β1, α-SMA, and COL1A1 expression (<0.05). In IUA rats, adiponectin improved uterine morphology, increased endometrial glands, reduced collagen fiber deposition, and downregulated NLRP3, IL-1β, and TGF-β1 expression (<0.05).

Discussion

Adiponectin alleviates endometrial inflammation and fibrosis in IUA, potentially by modulating the NLRP3/IL-1β/TGF-β1 signaling pathway. These findings highlight adiponectin’s role in mitigating IUA progression and provide a theoretical basis for its clinical applications.

Conclusion

Adiponectin reduces inflammation and fibrosis in IUA by suppressing the NLRP3/IL-1β/TGF-β1 axis, offering new insights for IUA treatment strategies.

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2025-11-24
2026-01-30

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/content/journals/cmm/10.2174/0115665240435678251124061235
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Adiponectin Ameliorates Intrauterine Adhesion-Related Endometrial Inflammation and Fibrotic Changes by Downregulating the NLRP3/IL-1β/TGF-β1 Axis
Bentham Science Publishers ; https://doi.org/10.2174/0115665240435678251124061235
/content/journals/cmm/10.2174/0115665240435678251124061235
/content/journals/cmm/10.2174/0115665240435678251124061235
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  • Article Type:     Research Article
Keywords: TGF-β1 ; Adiponectin ; IL-1β ; NLRP3 ; Intrauterine Adhesions

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