All-Trans Retinoic Acid Attenuates Hypoxia-Induced Injury in NRK52E Cells via Inhibiting NF-κB/VEGF and TGF-β2/VEGF Pathway

Abstract

Background/Aims: Hypoxia has recently been proposed as one of the most important factors in progressive renal injury. Hypoxia-induced vascular endothelial growth factor (VEGF) expression may play a critical role in maintaining peritubular capillary endothelium in renal disease. This study was designed to investigate the effect and underlying mechanism of all-trans retinoic acid (ATRA) on hypoxia-induced injury in NRK52E cells. Methods: For mimicking hypoxia, cells were treated with 100 µM of cobalt chloride (CoCl2). The cell viability, expression of VEGF, p65, transforming growth factor-β2 (TGF-β2) and serine carboxypeptidase 1 (Scpep1), and nuclear factor of kappaB (NF-κB) activities after ATRA treatment were determined by MTT, western blot and electrophoretic mobility shift assay. Co-immunoprecipitation analysis was performed to demonstrate whether Scpep1 interacted with TGF-β2. Results: It was found that CoCl2 triggered hypoxia injury and significantly reduced cell viability. ATRA pretreatment increased the cell survival rate. Under hypoxic conditions, the expression of VEGF, p65 and TGF-β2 increased. Addition of ATRA significantly attenuated the expression of VEGF, p65 and TGF-β2. There was a corresponding variation of NF-κB/DNA binding activities. In addition, ATRA stimulated Scpep1 expression under normoxic and hypoxia condition. Furthermore, TGF-β2 interacted with Scpep1. Conclusions: This study indicated that ATRA may attenuate hypoxia-induced injury in NRK52E cells via inhibiting NF-κB/VEGF and TGF-β2/VEGF pathway.