JAZF1 is transcriptionally regulated by SOX11 and promotes cardiac fibrosis by PI3K-Akt pathway

Abstract

Cardiac fibrosis is a component of all chronic heart diseases. JAZF1 regulates metabolism through various mechanisms; however, its role in cardiac fibrosis remains unclear. We aimed to investigate the role of JAZF1 in cardiac fibrosis. A rat cardiac fibrosis model was established by administering isoproterenol subcutaneously for 14 days (5 mg/kg/day); an equal volume of saline was administered to the control group. Cardiac fibroblasts were treated with TGF-β1 for 48 h to mimic cardiac fibrosis in vitro. JAZF1 expression at the protein and mRNA levels was enhanced in CFs and cardiac fibrosis tissues. JAZF1 downregulation suppressed CFs' proliferation and migration. Western blotting showed that the PI3K/Akt signaling pathway was significantly decreased after JAZF1 knockdown. Further experiments revealed that SOX11 is an important transcription factor whose overexpression and downregulation enhanced and suppressed JAZF1 levels, respectively. Luciferase analysis showed that SOX11 interacted with the JAZF1 promoter. Moreover, SOX11 promoted cardiac fibrosis by regulating JAZF1 expression. JAZF1 was enhanced in cardiac fibrosis tissue and TGF-β-treated CFs. JAZF1 knockdown decreased CFs' migration and proliferation, possibly remediated by SOX11 with activation of PI3k/Akt signaling pathways.