Altered Expression of Tight Junction Proteins in Cyclosporine Nephrotoxicity
- Authors
- Lee, Chang Hwa; Kim, Sua; Kang, Chong Myung; Kim, Wan Young; Kim, Jin; Kim, Gheun-Ho
- Issue Date
- 2011
- Publisher
- KARGER
- Keywords
- Cyclosporine nephrotoxicity; Paracellular permeability; Sodium chloride symporter; Tight junction proteins; WNK4 protein
- Citation
- AMERICAN JOURNAL OF NEPHROLOGY, v.33, no.1, pp.7 - 16
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF NEPHROLOGY
- Volume
- 33
- Number
- 1
- Start Page
- 7
- End Page
- 16
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/169419
- DOI
- 10.1159/000322445
- ISSN
- 0250-8095
- Abstract
- Background/Aims: The increased permeability of chloride in the distal cortical nephron in cyclosporine nephrotoxicity may involve the transcellular pathway mediated by the thiazide-sensitive Na+-Cl- cotransporter and/or the paracellular pathway mediated by the tight junctions (TJs). Methods: 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 (Delta TER). Results: Cyclosporine treatment induced a decrease in Na+-Cl- 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, Delta TER of MDCK monolayers was decreased by 100 ng/ml cyclosporine. Conclusion: 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.
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