Transcriptional up-regulation of relaxin-3 by Nur77 attenuates β-adrenergic agonist-induced apoptosis in cardiomyocytes

The Journal of Biological Chemistry
Xiaohua YouJianxin Sun

Abstract

The relaxin family peptides have been shown to exert several beneficial effects on the heart, including anti-apoptosis, anti-fibrosis, and anti-hypertrophy activity. Understanding their regulation might provide new opportunities for therapeutic interventions, but the molecular mechanism(s) coordinating relaxin expression in the heart remain largely obscured. Previous work demonstrated a role for the orphan nuclear receptor Nur77 in regulating cardiomyocyte apoptosis. We therefore investigated Nur77 in the hopes of identifying novel relaxin regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) data indicated that ectopic expression of orphan nuclear receptor Nur77 markedly increased the expression of latexin-3 (RLN3), but not relaxin-1 (RLN1), in neonatal rat ventricular cardiomyocytes (NRVMs). Furthermore, we found that the β-adrenergic agonist isoproterenol (ISO) markedly stimulated RLN3 expression, and this stimulation was significantly attenuated in Nur77 knockdown cardiomyocytes and Nur77 knockout hearts. We showed that Nur77 significantly increased RLN3 promoter activity via specific binding to the RLN3 promoter, as demonstrated by electrophoretic mobility shift assay (EMSA) and chr...Continue Reading

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Citations

Nov 13, 2019·PloS One·Julie Birkmose AxelsenAsger Andersen
Aug 29, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ni ZhuJianxin Sun
Aug 8, 2021·International Journal of Molecular Sciences·Ana ParedesMercedes Ricote

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