Altered Expression of Alpha(2)beta(1) Integrin in Kidney Fibroblasts: A Potential Mechanism for CsA-induced Nephrotoxicity

作者：Zal Fatemeh; Mostafavi Pour Zohreh^*; Moattari Afagh; Sardarian Ahmadreza; Vessal Mahmood

来源：Archives of Iranian Medicine, 2014, 17(8): 556-562.

• Alpha(2)beta(1) integrin
• cyclosporine A
• nephrotoxicity
• Quercetin
• Vitamin E

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 canto deemed pivotal. The-objective of the present study was to observe the expression levels of alpha2beta1 integrin-following CsA treatment +/- antioxidants. %26lt;br%26gt;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 alpha(2) and beta(1) integrins. %26lt;br%26gt;Results: We found that alpha(2) and beta(1) 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%. %26lt;br%26gt;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.

• 出版日期2014-8