miR-374 promotes myocardial hypertrophy by negatively regulating vascular endothelial growth factor receptor-1 signaling
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Vascular endothelial growth factor (VEGF) is an essential cytokine that has functions in the formation of new blood vessels and regression of cardiac hypertrophy. VEGF/VEGFreceptor- 1 (VEGFR1) signaling plays a key role in the regression of cardiac hypertrophy, whereas VEGF/VEGFR2 signaling leads to cardiac hypertrophy. In this study, we identified the prohypertrophic role of miR-374 using neonatal rat ventricular myocytes (NRVMs). Our results showed that overexpression of miR-374 activated G protein-coupled receptor-mediated prohypertrophic pathways by the inhibition of VEGFR1-dependent regression pathways. Luciferase assays revealed that miR-374 could directly target the 3’-untranslated regions of VEGFR1 and cGMP-dependent protein kinase-1. Collectively, these findings demonstrated that miR-374 was a novel pro-hypertrophic microRNA functioning to suppress the VEGFR1-mediated regression pathway.
Abstract
Vascular endothelial growth factor (VEGF) is an essential cytokine that has functions in the formation of new blood vessels and regression of cardiac hypertrophy. VEGF/VEGFreceptor- 1 (VEGFR1) signaling plays a key role in the regression of cardiac hypertrophy, whereas VEGF/VEGFR2 signaling leads to cardiac hypertrophy. In this study, we identified the prohypertrophic role of miR-374 using neonatal rat ventricular myocytes (NRVMs). Our results showed that overexpression of miR-374 activated G protein-coupled receptor-mediated prohypertrophic pathways by the inhibition of VEGFR1-dependent regression pathways. Luciferase assays revealed that miR-374 could directly target the 3’-untranslated regions of VEGFR1 and cGMP-dependent protein kinase-1. Collectively, these findings demonstrated that miR-374 was a novel pro-hypertrophic microRNA functioning to suppress the VEGFR1-mediated regression pathway.
참고문헌 (24)
- Frey N, "Cardiac hypertrophy: the good, the bad, and the ugly", Annu Rev Physiol, 65, pp.45~79 (2003)
- Rockman HA, "Seventransmembrane- spanning receptors and heart function", Nature, 415, pp.206~212 (2002)
- Heineke J, "Regulation of cardiac hypertrophy by intracellular signalling pathways", Nat Rev Mol Cell Biol, 7, pp.589~600 (2006)
- Ferrara N, "Molecular and biological properties of vascular endothelial growth factor", J Mol Med, 77, pp.527~543 (1999)
- Zhou Y, "Copper reverses cardiomyocyte hypertrophy through vascular endothelial growth factor-mediated reduction in the cell size", J Mol Cell Cardiol, 45, pp.106~117 (2008)
- Zhou Y, "Copper-induced regression of cardiomyocyte hypertrophy is associated with enhanced vascular endothelial growth factor receptor-1 signalling pathway", Cardiovasc Res, 84, pp.54~63 (2009)
- Olsson AK, "VEGF receptor signalling - in control of vascular function", Nat Rev Mol Cell Biol, 7, pp.359~371 (2006)
- Cantley LC, "The phosphoinositide 3-kinase pathway", Science, 296, pp.1655~1657 (2002)
- Takahashi T, "VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells", Oncogene, 18, pp.2221~2230 (1999)
- Lai EC, "Micro RNAs are complementary to 3' UTR sequence motifs that mediate negative post-transcriptional regulation", Nat Genet, 30, pp.363~364 (2002)
- Wang J, "Overview of MicroRNAs in Cardiac Hypertrophy, Fibrosis, and Apoptosis", Int J Mol Sci, 17, pp.749~769 (2016)
- Kim JO, "miR-185 plays an anti-hypertrophic role in the heart via multiple targets in the calcium-signaling pathways", PLoS One, 10, pp.e0122509~ (2015)
- Small EM, "Pervasive roles of microRNAs in cardiovascular biology", Nature, 469, pp.336~342 (2011)
- Ganesan J, "MiR-378 controls cardiac hypertrophy by combined repression of mitogen-activated protein kinase pathway factors", Circulation, 127, pp.2097~2106 (2013)
- Castaldi A, "MicroRNA- 133 modulates the 1-adrenergic receptor transduction cascade", Circ Res, 115, pp.273~283 (2014)
- Song DW, "The miR-19a", b family positively regulates cardiomyocyte hypertrophy by targeting atrogin-1 and MuRF-1, 2014, pp.457, 151~162
- Carmeliet P, "Molecular basis of angiogenesis. Role of VEGF and VE-cadherin", Ann N Y Acad Sci, 902, pp.249~262 (2000)
- Neufeld G, "Vascular endothelial growth factor (VEGF) and its receptors", FASEB J, 13, pp.9~22 (1999)
- Shiojima I, "Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure", J Clin Invest, 115, pp.2108~2118 (2005)
- Gray DB, "A nitric oxide", cyclic GMP-dependent protein kinase pathway alters transmitter release and inhibition by somatostatin at a site downstream of calcium entry, 1999, pp.72, 1981~1990
- O'Neil RG, "VASP: a TRPC4-associated phosphoprotein that mediates PKG-induced inhibition of storeoperated calcium influx", Am J Physiol Renal Physiol, 293, pp.F1766~F1767 (2007)
- Tang KM, "Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure", Nat Med, 9, pp.1506~1512 (2003)
- Vandael DH, "Cav1.3 and Cav1.2 channels of adrenal chromaffin cells: emerging views on cAMP", cGMP-mediated phosphorylation and role in pacemaking, 2012, pp.1828, 1608~1618
- Jeong MH, "Cucurbitacin I Attenuates Cardiomyocyte Hypertrophy via Inhibition of Connective Tissue Growth Factor (CCN2) and TGF- ", Smads Signalings, 2015, pp.10, e0136236~
