MicroRNA-129-5p targets keap-1 to protect against cardiomyocyte hypertrophy via Nrf2 pathway

Abstract Background: Cardiac hypertrophy is a common pathological process of many cardiac diseases and persistent cardiac hypertrophy is the main cause of heart failure and sudden cardiogenic death. It is of great value to elucidate the mechanism of cardiac hypertrophy for better prevention and treatment. Methods: The protein levels were measured by western blotting or RT-qPCR. cardiomyocytes hypertrophy was evaluated by [3H]-leucine incorporation assay. oxidative stress was measured by corresponding detection kits. The target relationship was measured by Luciferase reporter gene assay. Morphological change of cardiomyocyte was measured by immunofluorescence staining. Results: In our study, we for the first time revealed the effects and regulatory mechanism of miR-296-5p in cardiac hypertrophy in vitro . We found suppressed expression of miR-129-5p and elevated expression of keap-1 in Ang II-induced cardiomyocyte hypertrophy model. MiR-129-5p mimic effectively suppressed Ang II-induced hypertrophic responses and oxidative stress. Further experiments showed that keap-1 is a target of miR-129-5p, and miR-129-5p inhibitor promoted cardiomyocyte hypertrophy and oxidative stress by elevating keap-1. Besides, si-keap-1 mediated the activation of Nrf2 pathway, while miR-129-5p inhibitor inactivated the Nrf2 pathway by further elevating keap-1. Conclusions: MiR-129-5p mimic protects against Ang II induced cardiomyocyte hypertrophy via activating Nrf2 pathway by targeting keap-1.