system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, RESULTS. Meshes: Animals, Atrial Natriuretic Factor, Binding Sites, Cardiomegaly, Disease Models, Animal, GATA6 Transcription Factor, Gene Expression Regulation, Genotype, HEK293 Cells, Humans, Male, Metformin, Mice, Inbred C57BL, Mice, Knockout, Myocytes, Cardiac, Phenotype, Promoter Regions, Genetic, RNA Interference, Rats, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Transfection.
user
Does small heterodimer partner block cardiac hypertrophy by interfering with GATA6 signaling? Context: Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA-binding domain. Through interactions with other transcription factors, SHP regulates diverse biological events, including glucose metabolism in liver. However, the role of SHP in adult heart diseases has not yet been demonstrated. We aimed to investigate the role of SHP in adult heart in association with cardiac hypertrophy. The roles of SHP in cardiac hypertrophy were tested in primary cultured cardiomyocytes and in animal models. SHP-null mice showed a hypertrophic phenotype. Hypertrophic stresses repressed the expression of SHP, whereas forced expression of SHP blocked the development of hypertrophy in cardiomyocytes. SHP reduced the protein amount of Gata6 and, by direct physical interaction with Gata6, interfered with the binding of Gata6 to GATA-binding elements in the promoter regions of natriuretic peptide precursor type A. Metformin, an antidiabetic agent, induced SHP and suppressed cardiac hypertrophy. The metformin-induced antihypertrophic effect was attenuated either by SHP small interfering RNA in cardiomyocytes or in SHP-null mice.
assistant
These results establish SHP as a novel antihypertrophic regulator that acts by interfering with GATA6 signaling. SHP may participate in the metformin-induced antihypertrophic response. Final Decision: yes