1. Insulin‐like growth factor (IGF)‐I plays an important role in the pathogenesis of heart disease and has been shown to strongly induce the proliferation of cardiac fibroblasts (CFs). It remains unknown whether 14‐3‐3 proteins, which are associated the regulation of signal transduction, affect IGF‐I‐induced CF proliferation.
2. In the present study, we investigated the effects of 14‐3‐3 proteins on CF proliferation in response to IGF‐I. Proliferation of CFs was determined by cell counting and a bromodeoxyuridine incorporation assay. Phosphorylation of signalling molecules was evaluated by western blottling. Activity of nuclear factor of activated T cells (NFAT) was examined using a dual luciferase reporter gene assay and immunofluorescence.
3. It was found that adenovirus‐mediated transfection of YFP‐R18 peptide (AdR18), a known inhibitor of 14‐3‐3, significantly enhanced IGF‐I‐induced CF proliferation. This potentiation arose from an increase in phosphorylation of phosphatidylinositol 3‐kinase (PI3‐K) and AKT (protein kinase B), inactivation of glycogen synthesis kinase (GSK) 3β and increased NFAT activity.
4. Collectively, the results of the present study suggest that 14‐3‐3 proteins inhibit IGF‐I‐induced CF proliferation via a PI3‐K‐dependent NFAT signalling pathway. This finding may contribute to our understanding of the function of 14‐3‐3 proteins in the heart.