Clusterin expression and apoptosis in tissue remodeling associated with renal regeneration

Gobe, G. C., Buttyan, R., Wyburn, K. R. L., Etheridge, M. R. and Smith, P. J. (1995) Clusterin expression and apoptosis in tissue remodeling associated with renal regeneration. Kidney International, 47 2: 411-420. doi:10.1038/ki.1995.54

Author Gobe, G. C.
Buttyan, R.
Wyburn, K. R. L.
Etheridge, M. R.
Smith, P. J.
Title Clusterin expression and apoptosis in tissue remodeling associated with renal regeneration
Journal name Kidney International   Check publisher's open access policy
ISSN 0085-2538
Publication date 1995-02-01
Year available 1995
Sub-type Article (original research)
DOI 10.1038/ki.1995.54
Open Access Status Not yet assessed
Volume 47
Issue 2
Start page 411
End page 420
Total pages 10
Place of publication London, United Kingdom
Publisher Nature
Language eng
Abstract To analyze the role of clusterin in renal diseases involving a regenerative process, we have used a novel rodent model to compare temporal and spatial expression of clusterin mRNA. Thus, renal artery stenosis was used to induce unilateral non-infarctive renal atrophy. After several weeks, when cellular pathology of atrophic kidneys involved minimal apoptosis or inflammatory response and mitosis was at normal levels, regeneration of atrophic kidneys was stimulated by removal of the contralateral healthy kidneys. The regrowth response was very rapid and involved renal hyperplasia rather than hypertrophy. Regenerating kidneys were studied 0, 4, 8, 24 hours and 2, 3, 5, 7, and 14 days after contralateral nephrectomy. Several parameters were compared: level and localization of clusterin mRNA; cell proliferation; cell dedifferentiation and redifferentiation; and apoptosis. During the acute regenerative phase (first 24 hr) clusterin expression was markedly increased, decreasing to untraceable levels by five days of regeneration. Clusterin mRNA was localized in dilated or collapsed atrophic tubules that had lost identifying surface structures of normal tubular epithelium (termed dedifferentiated). Clusterin was also localized in the periphery of some blood vessel walls. Cell proliferation peaked at three to five days of regeneration, and was also localized in dedifferentiated tubules. Despite the regenerative stimulus, an unexpected result was a transient but marked increase in apoptotic cell death in atrophic tubules in the first 24 hours of regeneration. Our results provide evidence of a temporal association between increased clusterin expression and apoptosis, but in situ localization showed clusterin mRNA over apparently viable, as well as apoptotic, cells in the epithelium of tubules showing clusterin expression. Clusterin mRNA was rarely identified over epithelial cells in foci of non-atrophic (non-dedifferentiated) nephrons that responded to the regenerative stimulus by cellular hypertrophy. The dramatic response after initiation of regeneration, especially the initiation of apoptosis in the tubular epithelium, may have applications for the study of genetic changes leading to renal oncogenesis.
Keyword Urology & Nephrology
Urology & Nephrology
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 45 times in Thomson Reuters Web of Science Article | Citations
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