The mechanism of all- trans retinoic acid in the regulation of apelin expression in vascular endothelial cells

• Published in: Bioscience reports 2017-12, Vol.37 (6)
• Main Authors: Shi, Hongyun, Yuan, Lanhui, Yang, Huibin, Zang, Aimin
• Format: Article
• Language: English
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/bsr20170684

The gene can promote vascular endothelial cell (VEC) proliferation, migration, and angiogenesis. However, the molecular mechanism for regulation of the gene is still unknown. Real-time PCR and Western blotting analysis were employed to detect the effect of all- retinoic acid (ATRA) in up-regulating apelin expression in human umbilical vein endothelial cells (HUVECs). Furthermore, the 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.