Journal
EXPERIMENTAL AND MOLECULAR PATHOLOGY
Volume 70, Issue 1, Pages 43-53Publisher
ACADEMIC PRESS INC
DOI: 10.1006/exmp.2000.2346
Keywords
aging; senescence; TGF-beta; p21; tubulointerstitial fibrosis
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Funding
- NIDA NIH HHS [R01 DA 12111] Funding Source: Medline
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Kidney aging has been recognized as a chronic process of compromised renal function and structural changes in the tubulointerstitium and glomerulus. Cell senescence is associated with alterations in cell structure and function, including expression of cytokines and structural and regulatory components of extracellular matrix proteins. In this investigation, we tested the hypothesis that senescent renal cells may accumulate in vivo with advancing age. We also evaluated the expression of transforming growth factor (TGF)-beta1 and p21(WAF1/CIP1) in aging kidneys. Sprague-Dawley rats at the ages of 3, 12, and 24 months were used for this study. Renal tissues were processed for morphometric and senescence analysis. Expression of TGF-beta1 and p21(WAF/CIP1) was evaluated by Northern or Western blot analysis and immunohistochemistry. Substantial tubulointerstitial injury occurred at the age of 12 months, but significant glomerular structure alteration was observed at the age of 24 months. Tubular cells developed senescence, which was detected by beta -galactosidase staining. This staining increased in frequency and intensity with age. Renal cortices showed a significant increase in the mRNA expression for TGF-beta1 and protein level for p21(WAF1/CIP1). The enhanced expression of TGF-beta1 and p21(WAF1/CIP1) was localized in the tubulointersititial cells. These data suggest that tubular cells undergo senescence and express increased TGF-beta1 and p21(WAF1/CIP1). With advancing age. These age-related cellular and molecular alterations may play an important role in the initiation and/or progression of tubulointerstitial fibrosis and glomerulosclerosis in aging. (C) 2001 Academic Press.
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