{"paper_id":"252bc511-5b9f-4f12-91a0-21b034f8d9dd","body_text":"Abstract\nEndometriosis, an atypical benign disorder, may disrupt epithelial-mesenchymal transition (EMT) due to a dysregulated balance between matrix metalloproteinases (MMPs) and their inhibitors. Ramipril, an angiotensin converting enzyme (ACE) inhibitor, is crucial in mediating angiogenesis, inflammation, oxidative stress, and apoptosis. In the current work, we investigated how ramipril modulates EMT in endometriosis rats. Five adult virgin female Wistar rats were donor rats, and thirty rats were randomly divided into three groups following peritoneal uterine tissue transplantation (group 2 and group 3). The sham control group was group 1. Morphological alterations were predominantly assessed through hematoxylin–eosin (H-E) staining, succeeded by the immunoreactivity analysis of MMP9, tissue inhibitor of metalloproteinases 1 (TIMP1), reversion-inducing cysteine-rich protein with Kazal motifs (RECK), epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), and vimentin in the uteri and ectopic lesions of the specified groups. Zymography was conducted to assess the activities of MMP9 and MMP2. Immunoblotting was subsequently conducted for MMP9, TIMP1, snail, E-cadherin, N-cadherin, and vimentin in both uteri and ectopic lesions. Immunoblotting was conducted for phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), mechanistic target of rapamycin (mTOR), p70 ribosomal S6 kinase 1 (S6K1), and hypoxia-inducible factor 1-alpha (HIF-1ɑ) in the ectopic lesions. A significant reduction in the average quantity of ectopic endometrial glands was recorded in group 3. A significant decrease in the expressions of MMP9:TIMP1 (RECK) ratios (p = 0.00012; p = 0.001), snail, p-PI3K, p-AKT, p-mTOR, p-S6K1, and HIF-1ɑ (p < 0.05) proteins was observed in the ectopic lesions of group 3. A significant increase in the E-cadherin to N-cadherin (vimentin) ratios (p = 0.001) was observed in group 3 ectopic lesions. In conclusion, the administration of ramipril led to the reversal of EMT-like process by disrupting the MMP9/PI3K/AKT/S6K1 pathway in rats induced with endometriosis.\nSimilar content being viewed by others\nData availability\nThe corresponding author can provide the datasets used in this study upon reasonable request.\nAbbreviations\n- ACE :\n-\nAngiotensin converting enzyme\n- AP :\n-\nAlkaline phosphatase\n- BCA :\n-\nBicinchoninic acid method\n- BCIP :\n-\n5-Bromo-4-chloro-3-indoyl-phosphate\n- BSA :\n-\nBovine serum albumin\n- EMT :\n-\nEpithelial-mesenchymal transition (EMT)\n- ECM :\n-\nExtracellular matrix\n- H-E :\n-\nHematoxylin-eosin\n- HRP :\n-\nHorseradish peroxidase\n- HIF-1ɑ :\n-\nHypoxia-inducible factor 1-alpha\n- MMPs :\n-\nMatrix metalloproteinases\n- mTOR :\n-\nMechanistic target of rapamycin\n- NBT :\n-\nNitro blue tetrazolium\n- OVX :\n-\nOvariectomy\n- PBS :\n-\nPhosphate buffered saline\n- PI3K :\n-\nPhosphoinositide 3-kinase\n- RECK :\n-\nReversion-inducing cysteine-rich protein with Kazal motifs\n- RIPA :\n-\nRadioimmunoprecipitation assay buffer\n- TIMP1 :\n-\nTissue inhibitor of metalloproteinases 1\n- TFs :\n-\nTranscription factors\n- S6K1 :\n-\nP70 ribosomal S6 kinase 1\nReferences\nBarthelmebs M, Michele G, Jean-Louis L (1995) Ramipril-induced decrease in renal lithium excretion in the rat. 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No.: UGCES-22-GE-WES-F-SJSGC-4185.\nFunding\nThis work was supported by a grant from the scientific project {1198(Sanc.)/STBT-11012(15)}, funded by the Department of Science and Technology and Biotechnology, West Bengal, India. We are thankful to DBT-BUILDER (BT/INF/22/SP45088/2022) for instrumental and infrastructural facilities and DST-FIST, Govt. of India for other infrastructural facilities to the Life Sciences department (SR/FST/LSI-560/2013).\nAuthor information\nAuthors and Affiliations\nContributions\nPM has conceptualised, researched, designed, executed the tests, analysed the results, and prepared the original draft. SSB has conceptualised, overseen, secured funding and laboratory resources, and revised the initial draft. 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Repurposing ramipril to mitigate EMT-like transition in endometriosis by PI3K/AKT/S6K1 signalling pathway: a study in endometriosis induced rats. Naunyn-Schmiedeberg's Arch Pharmacol 399, 9923–9936 (2026). https://doi.org/10.1007/s00210-026-05030-4\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s00210-026-05030-4","source_license":"CC0","license_restricted":false}