Abstract P2113: Zdhhc7 Uniquely Influences Cardiac Fibroblast Activity Amongst Golgi-localized S-acyltransferases

Cardiac fibroblasts (CF’s), the heart’s most critical regulators of the extra-cellular matrix, can undergo a continuum of activation states when stimulated that influence their proliferation, migration, collagen production, and cell-to-cell communication in response to injury. The signaling pathways that underlie this transformation though, are poorly understood. Previous studies have shown zDHHC3, an S-acyltransferase enzyme that mediates the reversible lipid modification, palmitoylation, to be important in cardiac remodeling in cardiomyocytes due to its ability to regulate intracellular signaling, though the role of zDHHC enzymes and palmitoylation in CF signaling are unknown. To investigate this, we deleted zDHHC3 or the closely related enzyme, zDHHC7, in cardiac fibroblasts to screen for changes in fibroblast activity and myocardial fibrosis. Loss of zDHHC7, but not zDHHC3, resulted in increased expression of the activated cardiac fibroblast marker α-smooth muscle actin in response to TGFb stimulation and a trend towards increased mRNA levels of fibrotic genes. More notably, zDHHC7 deletion significantly blunted migratory ability of adult cardiac fibroblasts in scratch assays. These data suggest zDHHC7 plays a critical role in CF signaling, and future experiments include analyzing the impact of zDHHC3/7 deletion alone or in combination on cardiac fibrosis and identifying key substrates and pathways being modified by these enzymes in CFs.