All-trans retinoic acid protects renal tubular epithelial cells against hypoxia induced injury in vitro.

X Wan, X Li, H Bo, Y Zhao, L Liu, W Chen, Z Yin, C Cao

Department of Nephrology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China.

Transplantation proceedings 2013 Mar

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It has been reported that the all-trans retinoic acid (atRA)-mediated protective effects in various cells are related to the inhibition of nuclear factor (NF)-κB activities. There exists some evidence that an increase in vascular endothelial growth factor (VEGF), which is expressed by proximal tubular epithelial cells and regulated by NFκB, may play a critical role in maintaining peritubular capillary endothelium in renal disease. By stimulating the production of VEGF, hypoxia is involved in tubulointerstitial fibrosis processes in various renal diseases. NRK52E cells survival rate was proportional to absorbance in dimethyl-thiazol-diphenyltetrazoliumbromide tests. Quantitative real-time polymerase chain reaction and Western blot were performed to assay the expression of VEGF, p65, and Scpep1. The activation of NFκB was determined by electrophoretic mobility shift assay. Co-immunoprecipitation analysis demonstrates that whether the Scpep1 and NFκB protein interacted. We demonstrated that the hypoxia-mimicking agent CoCl2 triggered hypoxia injury of rat proximal tubular epithelial cells and significantly reduced cell viability. Addition of atRA increased the cell survival rate. Under CoCl(2)-mimicking hypoxic conditions, the expression of VEGF and p65 increased. The addition of atRA significantly attenuated the expression of VEGF and p65. There was a similar variation of NFκB/DNA binding activities. atRA not only activated distinct pathways to stimulate the expression of Scpep1, a retinoid-inducible gene, under normoxic conditions, but also acted as a CoCl(2)-mimicking hypoxia. The protective effects of atRA against hypoxia-induced injury might be involved in suppression of VEGF expression via stimulating Scpep1 distinct pathways and inhibiting the NFκB pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

X Wan, X Li, H Bo, Y Zhao, L Liu, W Chen, Z Yin, C Cao. All-trans retinoic acid protects renal tubular epithelial cells against hypoxia induced injury in vitro. Transplantation proceedings. 2013 Mar;45(2):497-502