Calcineurin/NFATc3 pathway mediates myocardial fibrosis in diabetes by impairing enhancer of zeste homolog 2 of cardiac fibroblasts
BMC Cardiovascular Disorders, ISSN: 1471-2261, Vol: 23, Issue: 1, Page: 474
2023
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Wuxi People's Hospital Affiliated to Nanjing Medical University Researchers Add New Study Findings to Research in Calcineurin (Calcineurin/NFATc3 pathway mediates myocardial fibrosis in diabetes by impairing enhancer of zeste homolog 2 of ...)
2023 OCT 10 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Daily -- Investigators publish new report on calcineurin. According to
Article Description
Background: Diabetes is associated with myocardial fibrosis, while the underlying mechanisms remain elusive. The aim of this study is to investigate the underlying role of calcineurin/nuclear factor of activated T cell 3 (CaN/NFATc3) pathway and the Enhancer of zeste homolog 2 (EZH2) in diabetes-related myocardial fibrosis. Methods: Streptozotocin (STZ)-injected diabetic rats were randomized to two groups: the controlled glucose (Con) group and the diabetes mellitus (DM) group. Eight weeks later, transthoracic echocardiography was used for cardiac function evaluation, and myocardial fibrosis was visualized by Masson trichrome staining. The primary neonatal rat cardiac fibroblasts were cultured with high-glucose medium with or without cyclosporine A or GSK126. The expression of proteins involved in the pathway was examined by western blotting. The nuclear translocation of target proteins was assessed by immunofluorescence. Results: The results indicated that high glucose treatment increased the expression of CaN, NFATc3, EZH2 and trimethylates lysine 27 on histone 3 (H3K27me3) in vitro and in vivo. The inhibition of the CaN/NFATc3 pathway alleviated myocardial fibrosis. Notably, inhibition of CaN can inhibit the nuclear translocation of NFATc3, and the expression of EZH2 and H3K27me3 protein induced by high glucose. Moreover, treatment with GSK126 also ameliorated myocardial fibrosis. Conclusion: Diabetes can possibly promote myocardial fibrosis by activating of CaN/NFATc3/EZH2 pathway.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85171673081&origin=inward; http://dx.doi.org/10.1186/s12872-023-03492-5; http://www.ncbi.nlm.nih.gov/pubmed/37735624; https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-023-03492-5; https://dx.doi.org/10.1186/s12872-023-03492-5
Springer Science and Business Media LLC
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