In:
American Journal of Nephrology, S. Karger AG, Vol. 33, No. 1 ( 2011), p. 7-16
Abstract:
〈 i 〉 Background/Aims: 〈 /i 〉 The increased permeability of chloride in the distal cortical nephron in cyclosporine nephrotoxicity may involve the transcellular pathway mediated by the thiazide-sensitive Na 〈 sup 〉 + 〈 /sup 〉 -Cl 〈 sup 〉 – 〈 /sup 〉 cotransporter and/or the paracellular pathway mediated by the tight junctions (TJs). 〈 i 〉 Methods: 〈 /i 〉 Cyclosporine was subcutaneously administered to Sprague-Dawley rats for 6 (7.5 mg/kg body weight) and 2 (25 mg/kg body weight) weeks, and immunoblot analysis and immunohistochemistry were carried out from the kidneys. Electrically tight epithelial Madin-Darby canine kidney (MDCK) I cells were exposed to cyclosporine for 72 h to measure changes in transepithelial electrical resistance (ΔTER). 〈 i 〉 Results: 〈 /i 〉 Cyclosporine treatment induced a decrease in Na 〈 sup 〉 + 〈 /sup 〉 -Cl 〈 sup 〉 – 〈 /sup 〉 cotransporter in rat renal cortex. WNK4 protein was increased in both rat kidneys and MDCK I cells. Occludin was also increased in rat kidneys and MDCK I cells exposed to 100 ng/ml cyclosporine. In contrast, cyclosporine treatment induced a decrease in zonula occludens 1 protein abundance and no changes in claudin-1 and claudin-4 in both rat kidneys and MDCK I cells. As a measure of the barrier to small ions, ΔTER of MDCK monolayers was decreased by 100 ng/ml cyclosporine. 〈 i 〉 Conclusion: 〈 /i 〉 Renal TJ proteins are affected by cyclosporine treatment. Changes in TJ protein assembly induced by altered expression of WNK4, occludin, and zonula occludens 1 may affect paracellular permeability.
Type of Medium:
Online Resource
ISSN:
0250-8095
,
1421-9670
Language:
English
Publisher:
S. Karger AG
Publication Date:
2011
detail.hit.zdb_id:
1468523-1
