Junctophilin-2 Regulates Store-Operated Calcium Entry to Drive Cardiac Fibroblast Activation, Fibrotic Repair, and Angiogenesis After Myocardial Infarction

Calcium homeostasis in cardiac fibroblasts (CFs) are thought to play a critical role in myocardial repair and remodeling following injury. Junctophilin-2 (JP2) is a structural protein known to regulate intracellular calcium signaling and excitation-contraction coupling in cardiomyocytes. However, the role of JP2 in CF biology remains unexplored. To investigate the functional role of JP2 in CFs, we transduced primary CFs with adenoviruses expressing GFP, JP2, or a JP2 targetting shRNA and determined differentially expressed genes via RNA-sequencing. JP2 overepression and silencing had opposite effects on the expression of genes associated with fibrosis, migration, and cell division. Overall design: Primary mouse cardiac fibroblasts were cultured and transducing for 72 hrs with adenoviruses expressing GFP, JP2, and shJP2 before harvesting for RNA-seq profiling.