title: Altered expression of alpha 2 beta 1 integrin in kidney fibroblasts: a potential mechanism for CsA-induced nephrotoxicity.
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 α2 and β1 integrins.
  
  
  RESULTS
  We found that α2 and β1 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%.
  
  
  CONCLUSIONS
  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.
authors: 1)Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 2)Reproductive Biology group, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.zmostafavipour@yahoo.co.uk.
authors: Fatemeh
authors: F
authors: Zal
authors: 3)Maternal-fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 4)Recombinant Protein Laboratory, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Zohreh
authors: Z
authors: Mostafavi-Pour
authors: 5)Microbiology Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Afagh
authors: A
authors: Moattari
authors: Student Research Committee, Resident of Orthodontics, Department of Orthodontics, Dental School, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Ahmadreza
authors: A
authors: Sardarian
authors: Department of Biochemistry, Fars Science and Research Branch, Islamic Azad University, Fars, Iran.
authors: Mahmood
authors: M
authors: Vessal
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D038982:Integrin alpha2beta1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D011794:Quercetin / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D007166:Immunosuppressive Agents; D038982:Integrin alpha2beta1; D012333:RNA, Messenger; D014810:Vitamin E; D016572:Cyclosporine; D011794:Quercetin