Document Detail

Increased epithelial cell proliferation and abnormal extracellular matrix in rat polycystic kidney disease.
MedLine Citation:
PMID:  9621276     Owner:  NLM     Status:  MEDLINE    
Proliferation of renal tubular epithelial cells is considered a major factor leading to cyst formation in human polycystic kidney disease (PKD). The Han:SPRD rat model for inherited PKD permits a close scrutiny, especially for early stages of the disease, and shows numerous similarities to human autosomal dominant PKD (ADPKD). In this study, the exact in vivo proliferation rate in Han:SPRD rat kidneys was evaluated in a cell type-specific manner, using immunohistochemistry with antibody to proliferating cell nuclear antigen (PCNA). The proliferation index (PI; percentage of PCNA-positive cell nuclei) was determined in normal and cystically altered tissue, and a relationship between proliferative activity and alterations in extracellular matrix expression was established using in situ hybridization for collagen I and IV mRNA. Heterozygously affected rats (cy/+) showed strong increases of PI values in cystically altered nephron portions that were mostly derived from proximal tubule. Cell proliferation obviously preceded cyst formation, because early in the progression of the disease, the normal-appearing tubules from PKD kidneys had markedly increased PI values compared with healthy controls (14.1-fold in 3-mo-old rats and 11.9-fold in 12-mo-old rats; P < 0.05), whereas later stages revealed a more generalized cystic degeneration of the nephron, with increases in PI between 14- and 82-fold, depending on the respective category of cystic epithelia. In cysts with a distal phenotype, changes were less pronounced. No significant differences were encountered between the two age groups. Proliferation was also present in interstitial cells, whereas glomeruli were unchanged. Increases in epithelial and interstitial proliferation coincided with an overexpression of matrix compounds. For comparison, changes in homozygously affected rats (cy/cy) showed up to several hundred-fold elevated PI values. These results indicate that in the Han:SPRD model for ADPKD, cystic malformation of the nephron is preceded by and coincides with enhanced epithelial and interstitial cell proliferation. Altered cell-matrix interactions seem to be directly involved in the disruption of epithelial differentiation.
K Ramasubbu; N Gretz; S Bachmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  9     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-08-24     Completed Date:  1998-08-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  937-45     Citation Subset:  IM    
Department of Anatomy, Klinikum Mannheim, University of Heidelberg, Germany.
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MeSH Terms
Aging / physiology
Cell Division / physiology
Epithelial Cells / pathology
Extracellular Matrix / metabolism*
Kidney / pathology
Polycystic Kidney Diseases / genetics,  metabolism*,  pathology*
Proliferating Cell Nuclear Antigen / metabolism
Rats, Inbred Strains / genetics
Reg. No./Substance:
0/Proliferating Cell Nuclear Antigen

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