biostudies-literatureRath SKDZHK grantDFG grant119https://www.ebi.ac.uk/biostudies/studies/S-EPMC11350970biostudies-literatureUnknown16(1)<h4>Background</h4>Cardiac fibrosis is the hallmark of all forms of chronic heart disease. Activation and proliferation of cardiac fibroblasts are the prime mediators of cardiac fibrosis. Existing studies show that ROS and inflammatory cytokines produced during fibrosis not only signal proliferative stimuli but also contribute to DNA damage. Therefore, as a prerequisite to maintain sustained proliferation in fibroblasts, activation of distinct DNA repair mechanism is essential.<h4>Result</h4>In this study, we report that TET3, a DNA demethylating enzyme, which has been shown to be reduced in cardiac fibrosis and to exert antifibrotic effects does so not only through its demethylating activity but also through maintaining genomic integrity by facilitating error-free homologous recombinationClinical epigeneticsLoss of tet methyl cytosine dioxygenase 3 (TET3) enhances cardiac fibrosis via modulating the DNA damage repair response.PMC11350970ZE523/2-3MD23Zeisberg EMSchlosser DRath SKTampe BZeisberg MNyamsuren GYu DSMaamari SHulshoff MSfalseLoss of tet methyl cytosine dioxygenase 3 (TET3) enhances cardiac fibrosis via modulating the DNA damage repair response.<h4>Background</h4>Cardiac fibrosis is the hallmark of all forms of chronic heart disease. Activation and proliferation of cardiac fibroblasts are the prime mediators of cardiac fibrosis. Existing studies show that ROS and inflammatory cytokines produced during fibrosis not only signal proliferative stimuli but also contribute to DNA damage. Therefore, as a prerequisite to maintain sustained proliferation in fibroblasts, activation of distinct DNA repair mechanism is essential.<h4>Result</h4>In this study, we report that TET3, a DNA demethylating enzyme, which has been shown to be reduced in cardiac fibrosis and to exert antifibrotic effects does so not only through its demethylating activity but also through maintaining genomic integrity by facilitating error-free homologous recombination2024-01-01T00:00:00Z2024 Aug2026-04-16T03:23:00.447Z2025-04-05T18:34:18.262ZS-EPMC113509703919229910.1186/s13148-024-01719-6