Abstract | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
|
Authors | X Wan, X Li, H Bo, Y Zhao, L Liu, W Chen, Z Yin, C Cao |
Journal | Transplantation proceedings
(Transplant Proc)
Vol. 45
Issue 2
Pg. 497-502
(Mar 2013)
ISSN: 1873-2623 [Electronic] United States |
PMID | 23267795
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
Chemical References |
- Rela protein, rat
- Transcription Factor RelA
- Vascular Endothelial Growth Factor A
- vascular endothelial growth factor A, rat
- Cobalt
- Tretinoin
- Carboxypeptidases
- cobaltous chloride
|
Topics |
- Animals
- Blotting, Western
- Carboxypeptidases
(genetics, metabolism)
- Cell Hypoxia
- Cell Line
- Cell Survival
(drug effects)
- Cobalt
(pharmacology)
- Cytoprotection
- Dose-Response Relationship, Drug
- Electrophoretic Mobility Shift Assay
- Epithelial Cells
(drug effects, pathology)
- Fibrosis
- Gene Expression Regulation
(drug effects)
- Immunoprecipitation
- Kidney Tubules, Proximal
(drug effects, pathology)
- Rats
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
(drug effects)
- Transcription Factor RelA
(genetics, metabolism)
- Tretinoin
(pharmacology)
- Vascular Endothelial Growth Factor A
(genetics, metabolism)
|