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- W2891777345 abstract "Cardiac fibrosis is a common precursor to ventricular dysfunction and eventual heart failure, and cardiac fibrosis begins with cardiac fibroblast activation. Here we have demonstrated that the TGF-β signaling pathway and Wnt signaling pathway formed a transactivation circuit during cardiac fibroblast activation and that miR-384-5p is a key regulator of the transactivation circuit. The results of in vitro study indicated that TGF-β activated an auto-positive feedback loop by increasing Wnt production in cardiac fibroblasts, and Wnt neutralizing antibodies disrupted the feedback loop. Also, we demonstrated that miR-384-5p simultaneously targeted the key receptors of the TGF-β/Wnt transactivation circuit and significantly attenuated both TGF-β-induced cardiac fibroblast activation and ischemia-reperfusion-induced cardiac fibrosis. In addition, small molecule that prevented pro-fibrogenic stimulus-induced downregulation of endogenous miR-384-5p significantly suppressed cardiac fibroblast activation and cardiac fibrosis. In conclusion, modulating a key endogenous miRNA targeting multiple components of the TGF-β/Wnt transactivation circuit can be an effective means to control cardiac fibrosis and has great therapeutic potential." @default.
- W2891777345 created "2018-09-27" @default.
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- W2891777345 date "2018-09-11" @default.
- W2891777345 modified "2023-10-12" @default.
- W2891777345 title "Multipoint targeting of TGF-β/Wnt transactivation circuit with microRNA 384-5p for cardiac fibrosis" @default.
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- W2891777345 doi "https://doi.org/10.1038/s41418-018-0187-3" @default.
- W2891777345 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6748152" @default.
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