In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Mahmoudi, Mitra, Willgoss, Desley, Cuttle, Leila, Yang, Tao, Pat, Betty, Winterford, Clay, Endre, Zoltan, Johnson, David W., & Gobe, Glenda C. (2003) In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure. Journal of Pathology, 200(3), pp. 396-405.

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Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated.

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24 citations in Scopus
21 citations in Web of Science®
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ID Code: 67212
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Acute Kidney Injury/immunology/*metabolism, Animals, Apoptosis/physiology, Blotting, Western/methods, Caveolin 1, Caveolins/immunology/*physiology, Cell Adhesion/immunology, Cell Membrane/immunology/metabolism, Cytosol/metabolism, Disease Models, Animal, Immunohistochemistry/methods, Ischemia/immunology/physiopathology, Kidney/blood supply, Male, Membrane Proteins/analysis/immunology, Microscopy, Confocal/methods, Microscopy, Electron/methods, Rats, Rats, Sprague-Dawley
DOI: 10.1002/path.1368
ISSN: 0022-3417
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 26 Feb 2014 22:56
Last Modified: 25 Mar 2014 01:36

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