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Type: Artigo de periódico
Title: The Genetics Of Hypertension Modifies The Renal Cell Replication Response Induced By Experimental Diabetes.
Author: Silveira, Lilia A
Bacchi, Carlos E
Pinto, Glauce A
De Faria, José B Lopes
Abstract: To investigate whether the genetics of hypertension modifies renal cell responses in experimental diabetes, we studied the renal cell replication and its regulation by two cyclin-dependent kinase (Cdk) inhibitors, p27(Kip1) and p21(Cip1), in prehypertensive spontaneously hypertensive rats (SHR) and their genetically normotensive counterparts, Wistar Kyoto (WKY) rats, with and without streptozotocin-induced diabetes. In diabetic SHR, the number of proliferating glomerular (0.6 +/- 0.3 positive cells/50 glomeruli) and tubulointerstitial (2.8 +/- 0.6 positive tubulointerstitial cells/50 grid fields) cells assessed by the bromodeoxyuridine technique was significantly (P = 0.0002) lower than in control SHR (13.2 +/- 1.7 and 48.6 +/- 9.7, respectively) and control (14.0 +/- 1.8 and 63.9 +/- 10.6) and diabetic (14.3 +/- 3.5 and 66.4 +/- 11.5) WKY rats. Proliferating cell nuclear antigen, another marker of cell proliferation, was significantly reduced in replicating glomerular (P = 0.0002) and tubulointerstitial (P < 0.0001) cells in diabetic SHR. In freshly isolated glomeruli, the level of p27(Kip1) detected by Western blotting was significantly higher in diabetic SHR than in nondiabetic SHR (1.52 +/- 0.14 vs. 1.00 +/- 0.10% of control, P = 0.014). The expression of p21(Cip1) in isolated glomeruli did not differ among the groups of rats. In conclusion, the response of renal cell replication to diabetes differs markedly between prehypertensive SHR and their WKY control rats. The decreased glomerular cell proliferation in prehypertensive diabetic SHR is at least partly mediated by a higher expression of the Cdk inhibitor p27(Kip1).
Subject: Animals
Cell Cycle Proteins
Cell Division
Cyclin-dependent Kinase Inhibitor P21
Cyclin-dependent Kinase Inhibitor P27
Diabetes Mellitus, Experimental
Diabetic Nephropathies
Genetic Predisposition To Disease
Hypertension, Renal
In Situ Nick-end Labeling
Kidney Glomerulus
Organ Size
Rats, Inbred Shr
Rats, Inbred Wky
Tumor Suppressor Proteins
Citation: Diabetes. v. 51, n. 5, p. 1529-34, 2002-May.
Rights: fechado
Date Issue: 2002
Appears in Collections:Unicamp - Artigos e Outros Documentos

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