Regulation of MMP9 by MEF2A and STAT3 in Neonatal Rat Ventricular Cardiomyocytes

The myocyte enhancer factor-2 (MEF2) transcription factor is critical for defining cardiac-specific gene expression programs that have fundamental roles in differentiation and development. This thesis explored the effects of a novel protein:protein interaction between the MEF2A and signal transducer and activator of transcription-3 (STAT3) on matrix metalloproteinase (MMP9) transcriptional regulation in neonatal rat ventricular cardiomyocytes (NRVMs). Immunoprecipitation experiments confirmed a robust interaction between endogenous MEF2A and STAT3 within the NRVMs. SiRNA-mediated gene silencing and pharmacological inhibition revealed that MMP9 promoter activity, mRNA, and protein expression are significantly enhanced upon STAT3 depletion/inhibition and there is a marginal decrease in MMP9 mRNA upon MEF2A depletion. The foundational work in this thesis sheds light on the MMP9 gene transcriptional regulation by both MEF2A and STAT3, having implications for cardiac physiology and pathology associated with MMP9.