A novel mechanism regulating pyroptosis-induced fibrosis in endometriosis via lnc-MALAT1/miR-141-3p/NLRP3 pathway
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This study found that increased lnc-MALAT1 promotes pyroptosis and fibrosis in endometriosis by sponging miR-141-3p to upregulate NLRP3 expression.
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Abstract
Endometriosis is a chronic inflammatory disease distinguished by ectopic endometrium and fibrosis. NLRP3 inflammasome and pyroptosis are present in endometriosis. Aberrant increase of Long noncoding (Lnc)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a vital role in endometriosis. However, the relationship between lnc-MALAT1, pyroptosis, and fibrosis is not completely known. In the present study, we found that the pyroptosis levels in ectopic endometrium of patients with endometriosis were significantly increased, consistent with fibrosis levels. Lipopolysaccharide (LPS) + ATP could induce pyroptosis of primary endometrial stromal cells (ESCs), thereby releasing interleukin (IL)-1β and stimulating transforming growth factor (TGF)-β1-mediated fibrosis. NLRP3 inhibitor MCC950 had the same effect as TGF-β1 inhibitor SB-431542 in suppressing the fibrosis-inducing effect of LPS + ATP in vivo and in vitro. The abnormal increase of lnc-MALAT1 in ectopic endometrium was connected with NLRP3-mediated pyroptosis and fibrosis. Leveraging bioinformatic prediction and luciferase assays combined with western blotting and quantitative reverse transcriptase-polymerase chain reaction, we validated that lnc-MALAT1 sponges miR-141-3p to promote NLRP3 expression. Silencing lnc-MALAT1 in HESCs ameliorated NLRP3-mediated pyroptosis and IL-1β release, thereby relieving TGF-β1-mediated fibrosis. Consequently, our findings suggest that lnc-MALAT1 is critical for NLRP3-induced pyroptosis and fibrosis in endometriosis through sponging miR-141-3p, which may indicate a new therapeutic target of endometriosis treatment.
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Cited by (13)
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- AlkB Homolog 5 Regulates Hexokinase 2‐Mediated Glycolysis and Participates in the Progression of Endometriosis 2025
- Regulated cell death in endometrial diseases: from molecular mechanisms to targeted therapies 2025
- Hydrogen Sulfide Promotes Functional Endometrium Recovery via Regulating Pyroptosis in Severe Endometrial Injury: A Prospective Laboratory Based Randomized Control Trial 2025
- Endometriosis is not the endometrium: Reviewing the over-representation of eutopic endometrium in endometriosis research 2025
- The role of fibrosis in endometriosis: a systematic review 2024
- Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis 2024
- Regulated Cell Death in Endometriosis 2024
- Apparent lncRNAs involvement in pathogenesis of endometriosis 2024
- CHS-Ⅳa activates the IGF1R/PI3K signal pathway with inhibited pyroptosis of endometrial stromal cells and progress of endometriosis 2024
- Blocking GATA6 Alleviates Pyroptosis and Inhibits Abdominal Wall Endometriosis Lesion Growth Through Inactivating the PI3K/AKT Pathway 2024
- Role of the NLRP3 inflammasome in gynecological disease 2023
- Impaired bone morphogenetic protein signaling pathways disrupt decidualization in endometriosis 2023
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