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Irisin improves diabetic cardiomyopathy-induced cardiac remodeling by regulating GSDMD-mediated pyroptosis through MITOL/STING signaling
- Source :
- Biomedicine & Pharmacotherapy, Vol 171, Iss , Pp 116007- (2024)
- Publication Year :
- 2024
- Publisher :
- Elsevier, 2024.
-
Abstract
- Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM). However, the mechanisms underlying DCM-induced cardiac injury remain unclear. Recently, the role of cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling and pyroptosis in DCM has been investigated. Based on our previous results, this study was designed to examine the impact of irisin, mitochondrial ubiquitin ligase (MITOL/MARCH5), and cGAS/STING signaling in DCM-induced cardiac dysfunction and the effect of gasdermin D (GSDMD)-dependent pyroptosis. High-fat diet-induced mice and H9c2 cells were used for cardiac geometry and function or pyroptosis-related biomarker assessment at the end of the experiments. Here, we show that DCM impairs cardiac function by increasing cardiac fibrosis and GSDMD-dependent pyroptosis, including the activation of MITOL and cGAS/STING signaling. Our results confirmed that the protective role of irisin and MITOL was partially offset by the activation of cGAS/STING signaling. We also demonstrated that GSDMD-dependent pyroptosis plays a pivotal role in the pathological process of DCM pathogenesis. Our results indicate that irisin treatment protects against DCM injury, mitochondrial homeostasis, and pyroptosis through MITOL upregulation.
Details
- Language :
- English
- ISSN :
- 07533322
- Volume :
- 171
- Issue :
- 116007-
- Database :
- Directory of Open Access Journals
- Journal :
- Biomedicine & Pharmacotherapy
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.34a47f6284f24021ab90d5b378e649e4
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.biopha.2023.116007