Uridine-Cytidine Kinase 2 (UCK2)/Uridine-Cytidine Kinase Like 1 (UCKL1) complex exacerbates the differentiation of myocardial fibroblasts via TRIM21/Smurf2/Smad3 pathway after myocardial infarction.

ABSTRACT: Cardiac fibrosis following myocardial infarction (MI) is a pivotal driver of ventricular dysfunction and heart failure, yet the molecular checkpoints orchestrating the persistent activation of cardiac fibroblasts remain incompletely defined. Here, we uncover a non-canonical, metabolism-independent function of Uridine-Cytidine Kinase 2 (UCK2) and Uridine-Cytidine Kinase Like-1 (UCKL1) as synergistic regulators of pathological remodeling. We demonstrate that both proteins are robustly upregulated in the border zone of ischemic murine hearts and transforming growth factor-β (TGF-β)-activated human cardiac fibroblasts (HCFs). Mechanistically, UCK2 and UCKL1 physically assemble into an obligate functional complex that acts as a molecular scaffold rather than a metabolic enzyme. This complex rec

SUBMITTER: Zhou X 

PROVIDER: S-EPMC12745349 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature