Endothelial RNF20 suppresses endothelial-to-mesenchymal transition and safeguards physiological angiocrine signaling to prevent congenital heart disease.

ABSTRACT: Heart morphogenesis and function rely on intricate communication among distinct cardiac cell types. How their co-development and crosstalk are coordinated is largely unexplored. Our study unveils key functions of the histone H2B ubiquitin (H2Bub1) ligase RNF20 in second heart field development and cardiac endothelial cells. We demonstrate that RNF20 promotes Nrg1 expression through a RNF20-H2Bub1-dependent mechanism and restrains TGF-β signaling by influencing RNA polymerase II pause release at TGF-β target genes in endothelial cells. While heightened TGF-β signaling following RNF20 loss results endothelial-to-mesenchymal transition (EndMT), both impaired Nrg1 signaling and elevated TGF-β activity contribute to abnormal cardiomyocyte proliferation and contractility. Importantly, RNF20 expr

SUBMITTER: Dou Y 

PROVIDER: S-EPMC12559710 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature