MiR-25 suppresses 3T3-L1 adipogenesis by directly targeting KLF4 and C/EBPα.

In the past decade, miRNA emerges as a vital player in orchestrating gene regulation and maintaining cellular homeostasis. It is well documented that miRNA influences a variety of biological events, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes. It has been shown that adipogenesis is tightly modulated by a number of transcription factors such as PPARγ, KLF4, and C/EBPα. However, the molecular mechanisms underlying the missing link between miRNA and adipogenesis-related transcription factors remain elusive. In this study, we unveiled that miR-25, a member of miR-106b-25 cluster, was remarkably downregulated during 3T3-L1 adipogenesis. Restored expression of miR-25 significantly impaired 3T3-L1 adipogenesis and downregulated the expression of serial adipogenesis-related genes. Further experiments presented that ectopic expression of miR-25 did not affect cell proliferation and cell cycle progression. Finally, KLF4 and C/EBPα, two key regulators of adipocyte differentiation, were experimentally identified as bona fide targets for miR-25. These data indicate that miR-25 is a novel negative regulator of adipocyte differentiation and it suppressed 3T3-L1 adipogenesis by targeting KLF4 and C/EBPα, which provides novel insights into the molecular mechanism of miRNA-mediated cellular differentiation.

Effects of 3-aminobenzamide on ventricular function in infarct heart assessed by quantitative tissue velocity imaging.

BACKGROUND: Coronary artery disease is a common cardiovascular disease that often causes myocardial infarction (MI), which, after a certain period, can develop into congestive heart failure, resulting in high mortality and mortality rates. Overactivation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) has recently been considered a final common effector in myocardial ischemia/reperfusion injury. The aim of this study was to have a comprehensive understanding of the beneficial effects of 3-aminobenzamide (3-AB) on postinfarct myocardial injuries by inhibiting PARP. METHODS: A rat model of acute MI was established. Quantitative tissue velocity imaging technology in conjunction with conventional two-dimensional echocardiography and traditional pathological examinations was used to evaluate cardiac function. RESULTS: We observed detrimental alterations of cardiac morphology and function in MI hearts which were otherwise absent in sham-operated control rats. We found that 3-AB (30 mg/kg, i.p.) significantly restored MI-induced depression of the peak longitudinal systolic velocity in the left-ventricular anterior and lateral walls, and of the peak centripetal systolic velocity in the anterior septum, indicating that it improved the systolic function of the left ventricle. Administration of 3-AB significantly ameliorated MI-induced myocardial injuries as revealed by two-dimensional echocardiography, showing the improvement of multiple parameters including left-ventricular end-systolic diameter, left-ventricular end-diastolic diameter, end-diastolic volume, fractional shortening, left-ventricular ejection fraction, left-ventricular anterior wall end-diastolic thickness, and spherical index, indicating that it improved the overall cardiac structure and function. Additionally, 3-AB significantly reduced infarct size, MI-induced increase in left-ventricular mass, pathological score, and PARP overactivation. However, at the dosage tested in the present study, the improvement is in general moderate. CONCLUSION: Inhibition of PARP may be an alternative approach for improving cardiac function in the setting of MI, and quantitative tissue velocity imaging, combined with two-dimensional echocardiography, provides a more comprehensive, quantitative, rapid, noninvasive evaluation of global and regional cardiac function in rats.