MeCP2 triggers diabetic cardiomyopathy and cardiac fibroblast proliferation by inhibiting RASSF1A.

Diabetes causes cardiomyopathy and increases the risk of heart failure independent of hypertension and cardiac fibrosis disease. However, the molecular mechanism of cardiomyopathy caused by diabetic (DCM) is currently unknown. Here we explore the role of the Methyl CpG binding protein 2 (MeCP2) in DCM patients and a type 1 DM (T1DM) rat model. In this study, we employed streptozotocin (STZ)-induced rats DCM and DCM patient and found that MeCP2 triggers cardiac fibroblast proliferation in DCM by inhibiting of RASSF1A expression. Moreover, the in vitro study demonstrated that high glucose inhibited RASSF1A expression, accompanied by the increases of MeCP2 expression and DNA hypermethylation in RASSF1A promoter region. MeCP2 inhibition or knockdown reversed the decrease of RASSF1A transcription induced by high glucose in cardiac fibroblasts. MeCP2 triggers cardiac fibroblasts proliferation through the activation of RASSF1A/ERK1/2 signaling pathways. Our results demonstrated that MeCP2 plays a key role in RASSF1A mediated ERK1/2 activation in DCM. Taken together, these indicate that MeCP2 acts as a key regulator of DCM and cardiac fibroblasts proliferation.