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

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ZAL FATEMEH; MOSTAFAVI POUR ZOHREH; MOATTARI AFAGH; SARDARIAN AHMADREZA; VESSAL MAHMOOD

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Journal: ARCHIVES OF IRANIAN MEDICINE Year:2014 | Volume:17 | Issue:8 Page(s): 556-562

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Title

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

Author(s)

Keywords

ALPHA2BETA1 INTEGRIN

CYCLOSPORINE A

NEPHROTOXICITY

QUERCETIN

VITAMIN E

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.

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APA: Copy

ZAL, FATEMEH, MOSTAFAVI POUR, ZOHREH, MOATTARI, AFAGH, SARDARIAN, AHMADREZA, & VESSAL, MAHMOOD. (2014). ALTERED EXPRESSION OF ALPHA₂BETA₁ INTEGRIN IN KIDNEY FIBROBLASTS: A POTENTIAL MECHANISM FOR CSA-INDUCED NEPHROTOXICITY. ARCHIVES OF IRANIAN MEDICINE, 17(8), 556-562. SID. https://sid.ir/paper/281042/en

Vancouver: Copy

ZAL FATEMEH, MOSTAFAVI POUR ZOHREH, MOATTARI AFAGH, SARDARIAN AHMADREZA, VESSAL MAHMOOD. ALTERED EXPRESSION OF ALPHA₂BETA₁ INTEGRIN IN KIDNEY FIBROBLASTS: A POTENTIAL MECHANISM FOR CSA-INDUCED NEPHROTOXICITY. ARCHIVES OF IRANIAN MEDICINE[Internet]. 2014;17(8):556-562. Available from: https://sid.ir/paper/281042/en

IEEE: Copy

FATEMEH ZAL, ZOHREH MOSTAFAVI POUR, AFAGH MOATTARI, AHMADREZA SARDARIAN, and MAHMOOD VESSAL, “ALTERED EXPRESSION OF ALPHA₂BETA₁ INTEGRIN IN KIDNEY FIBROBLASTS: A POTENTIAL MECHANISM FOR CSA-INDUCED NEPHROTOXICITY,” ARCHIVES OF IRANIAN MEDICINE, vol. 17, no. 8, pp. 556–562, 2014, [Online]. Available: https://sid.ir/paper/281042/en

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