2026-10-13T15:38:56Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34038108 2026-10-01T04:25:17Z category_19 portal_316 item_type_3 month_year_10_2026

Supplementary file 1_PMEPA1 attenuates myocardial ischemia-reperfusion injury via interaction with NEDD4 and involvement of the TGF-β/SMAD pathway.docx Weilong Zhong (3329061) Yanan Li (94033) Baoze Qu (23848212) Pharmacology machine learning myocardial ischemia-reperfusion injury Nedd4 PMEPA1 protein-protein interaction Introduction<p>Myocardial ischemia-reperfusion injury (MIRI) remains a significant challenge in cardiovascular medicine, and its molecular mechanisms are not yet fully elucidated.</p>Methods<p>In the present study, integrated transcriptomic analysis combined with machine learning identified PMEPA1 as a key gene consistently downregulated in both rat models of MIRI and H9c2 cardiomyocytes subjected to ischemia –reperfusion injury. A series of in vivo and in vitro experiments, including gene overexpression and knockdown, cell viability and proliferation assays, flow cytometry, Western blot, co-immunoprecipitation, and immunofluorescence, were performed to investigate the role and underlying mechanism of PMEPA1 in MIRI.</p>Results<p>Overexpression of PMEPA1 enhanced cardiomyocyte proliferation, reduced apoptosis, and inhibited activation of the TGF-β/SMAD signaling pathway. Further investigation revealed a direct interaction between PMEPA1 and the E3 ubiquitin ligase NEDD4. Both NEDD4 overexpression and PMEPA1 knockdown aggravated cardiomyocyte injury and increased activation of the TGF-β/SMAD pathway. Notably, the detrimental effects of NEDD4 overexpression were attenuated in the absence of PMEPA1, suggesting a PMEPA1-dependent mechanism.</p>Discussion<p>These findings highlight a novel NEDD4–PMEPA1 axis in the regulation of TGF-β/SMAD signaling during myocardial injury and provide new insights into potential molecular targets for the treatment of cardiovascular disease.</p> 2026-10-01T04:25:17Z Dataset Dataset 10.3389/fphar.2026.1881951.s001 https://figshare.com/articles/dataset/Supplementary_file_1_PMEPA1_attenuates_myocardial_ischemia-reperfusion_injury_via_interaction_with_NEDD4_and_involvement_of_the_TGF-_SMAD_pathway_docx/34038108 CC BY 4.0