The mechanism of all-trans retinoic acid in the regulation of apelin expression in vascular endothelial cells
Open Access
- 12 December 2017
- journal article
- Published by Portland Press Ltd. in Bioscience Reports
- Vol. 37 (6)
- https://doi.org/10.1042/bsr20170684
Abstract
The apelin gene can promote vascular endothelial cell (VEC) proliferation, migration, and angiogenesis. However, the molecular mechanism for regulation of the apelin gene is still unknown. Real-time PCR and Western blotting analysis were employed to detect the effect of all-trans retinoic acid (ATRA) in up-regulating apelin expression in human umbilical vein endothelial cells (HUVECs). Furthermore, the in vivo study also indicated that ATRA could increase apelin expression in balloon-injured arteries of rats, which is consistent with the results from the cultured HUVECs. To ensure whether retinoic acid receptor (RAR) α (RARα) could be induced by ATRA in regulating apelin, the expression of RARα was tested with a siRNA method to knock down RARα or adenovirus vector infection to overexpress RARα. The results showed that ATRA could up-regulate apelin expression time- and dose- dependently in HUVECs. ATRA could induce a RARα increase; however, the expression of RARβ and RARγ were unchanged. The blocking of RARα signaling reduced the response of apelin to ATRA when HUVECs were treated with RARα antagonists (Ro 41-5253) or the use of siRNA against RARα (si-RARα) knockdown RARα expression before using ATRA. In addition, induction of RARα overexpression by infection with pAd-GFP-RARα further increased the induction of apelin by ATRA. These results suggested that ATRA up-regulated apelin expression by promoting RARα signaling.Keywords
This publication has 38 references indexed in Scilit:
- Overexpression of Angiopoietin-1 Increases CD133+/c-kit+ Cells and Reduces Myocardial Apoptosis in db/db Mouse Infarcted HeartsPLOS ONE, 2012
- Retinoic Acid Receptor α Mediates All-trans-retinoic Acid-induced Klf4 Gene Expression by Regulating Klf4 Promoter Activity in Vascular Smooth Muscle Cells*Online Journal of Public Health Informatics, 2012
- Hypoxia and proinflammatory factors upregulate apelin receptor expression in human stellate cells and hepatocytesGut, 2011
- HDAC2 phosphorylation-dependent Klf5 deacetylation and RARα acetylation induced by RAR agonist switch the transcription regulatory programs of p21 in VSMCsCell Research, 2011
- Upregulation of the apelin–APJ pathway promotes neointima formation in the carotid ligation model in mouseCardiovascular Research, 2010
- [Pyr 1 ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human HeartHypertension, 2009
- Regulation of the Hyaluronan Synthase 2 Gene by Convergence in Cyclic AMP Response Element-binding Protein and Retinoid Acid Receptor SignalingOnline Journal of Public Health Informatics, 2009
- Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosisJCI Insight, 2008
- Hypoxia-Induced Apelin Expression Regulates Endothelial Cell Proliferation and Regenerative AngiogenesisCirculation Research, 2008
- Apelin Stimulates Myosin Light Chain Phosphorylation in Vascular Smooth Muscle CellsArteriosclerosis, Thrombosis, and Vascular Biology, 2006