Baicalin protects against myocardial fibrosis through inhibition of DOT1L/COL-1 pathway during diabetic cardiomyopathy

Diabetic cardiomyopathy (DCM) requires a systematic approach for effective management. Focusing on key signaling pathways in myocardial fibrosis could offer novel therapeutic approaches for DCM. The objective of this research is to investigate new biomarker and the underlying mechanisms by which baicalin intervenes in the progression of DCM. Swiss Target Prediction databases and weighted correlation network analysis (WGCNA) were employed to collect and analyze targets of baicalin and DCM. Intersection targets were obtained through venn online website, network visualization was conducted through STRING database and Cytoscape 3.7.2 software. Molecular docking validation was completed via AutoDock Vina software. Western blotting, RT-qPCR and histology were carried out to validate the direct targets of baicalin and explore the molecular mechanism during DCM progression. In mice induced to DCM, we observed that disruptor of telomeric silencing 1-like (DOT1L) was upregulated. Baicalin (BC) reduced myocardial fibrosis in mice as indicated by the reduced expression levels of fibrosis markers COL-1 and TGF-β. The inhibitory effect of BC was reversed by overexpressed DOT1L and further enhanced by silenced DOT1L. Our results indicate that cardiomyocyte DOT1L exerts a pathogenic role in DCM and BC specifically targets DOT1L/COL-1 signaling to reduce myocardial fibrosis in DCM.