PMEPA1 attenuates myocardial ischemia-reperfusion injury via interaction with NEDD4 and involvement of the TGF-β/SMAD pathway
- 1Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical University , ,
- 2Department of Pediatrics, Jinzhou Maternal and Child Hospital , ,
Abstract
Introduction: Myocardial ischemia-reperfusion injury (MIRI) remains a significant challenge in cardiovascular medicine, and its molecular mechanisms are not yet fully elucidated.
Methods: 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.
Results: 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.
Discussion: 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.
Related
- Breviscapine attenuates myocardial ischemia-reperfusion injury by inhibiting ferroptosis via activation of NRF2/SLC7A11/GPX4 pathway
- Inclisiran attenuates myocardial ischemia/reperfusion injury by inhibiting macrophage M1 polarization
- Electroacupuncture pretreatment attenuates myocardial ischemia/reperfusion injury-induced ferroptosis via the p53/SLC7A11/GPX4 pathway
- ACSS2 phosphorylation at Ser659 attenuates neuronal apoptosis induced by cerebral ischemia-reperfusion by initiating autophagy
- Fetuin-A Attenuates HMGB1/TLR4-Mediated Ovarian Ischemia/Reperfusion Injury
BibTeX
@article{zhong2026pmepa1,
title = {{PMEPA1 attenuates myocardial ischemia-reperfusion injury via interaction with NEDD4 and involvement of the TGF-β/SMAD pathway}},
author = {Weilong Zhong and Yanan Li and Baoze Qu},
journal = {Frontiers in pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1881951},
url = {https://europepmc.org/article/PMC/PMC13668540},
note = {CC BY},
}
RIS
TY - JOUR
TI - PMEPA1 attenuates myocardial ischemia-reperfusion injury via interaction with NEDD4 and involvement of the TGF-β/SMAD pathway
AU - Weilong Zhong
AU - Yanan Li
AU - Baoze Qu
PY - 2026
DA - 2026/10/01
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1881951
UR - https://europepmc.org/article/PMC/PMC13668540
AB - Introduction: Myocardial ischemia-reperfusion injury (MIRI) remains a significant challenge in cardiovascular medicine, and its molecular mechanisms are not yet fully elucidated. Methods: 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. Results: 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. Discussion: 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.
SN - 1663-9812
ER -