Paper Information

Journal:   ARCHIVES OF IRANIAN MEDICINE   AUGUST 2014 , Volume 17 , Number 8; Page(s) 556 To 562.
 
Paper: 

ALTERED EXPRESSION OF ALPHA2BETA1 INTEGRIN IN KIDNEY FIBROBLASTS: A POTENTIAL MECHANISM FOR CSA-INDUCED NEPHROTOXICITY

 
 
Author(s):  ZAL FATEMEH, MOSTAFAVI POUR ZOHREH*, MOATTARI AFAGH, SARDARIAN AHMADREZA, VESSAL MAHMOOD
 
* DEPARTMENT OF BIOCHEMISTRY, SHIRAZ UNIVERSITY OF MEDICAL SCIENCES, SHIRAZ, IRAN
 
Abstract: 

BACKGROUND: Nephrotoxicity is considered a significant cause of patient morbidity following chronic Cyclosporine A (CsA) treatment. The exact mechanism of CsA-induced nephrotoxicity remains to be fully clarified. Tubulointerstitial fibrosis is widely regarded as a major pathway of CsA toxicity; therefore, the role of integrins as regulators of collagen in the extra-cellular matrix can be deemed pivotal. The objective of the present study was to observe the expression levels of alpha2beta1 integrin following CsA treatment +/- antioxidants.
METHODS: Adhesion assay, immunofluorescent and flow cytometric analyses were performed on kidney fibroblasts obtained from rats after administration of CsA (25 mg/kg/day) +/- Vitamin E (vit. E) and Quercetin (Q) for 4 weeks. Total RNA was collected from the aforementioned fibroblasts for semi-quantitative reverse transcriptase-polymerase chain reaction analysis of
a2 and b1 integrins.
RESULTS: We found that
a2 and b1 integrins were both markedly reduced following treatment with CsA, i.e., 25% and 13%, respectively, but were normal following subsequent consumption of the antioxidants vit. E and Q. Attachment and spreading of the CsA-treated fibroblasts declined from 82% to 50%; however, this effect was partially reversed to 70% following antioxidant treatment. Similar results were observed in the spreading assay in which the level of spreading decreased from 73% to 21% and was subsequently restored to 46%.
CONCLUSION: We conclude that cell adhesion, mediated by binding of integrin to collagen, which is a prerequisite of normal cell viability and collagen regulation, may be a novel pathway further explaining the nephrotoxic effects of CsA.

 
Keyword(s): ALPHA2BETA1 INTEGRIN, CYCLOSPORINE A, NEPHROTOXICITY, QUERCETIN, VITAMIN E
 
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