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Titolo:
Angiotensin converting-enzyme inhibitor treatment reduces glomerular p16(INK4) and p27(Kip1) expression in diabetic BBdp rats
Autore:
Wolf, G; Wenzel, U; Ziyadeh, FN; Stahl, RAK;
Indirizzi:
Univ Hamburg, Dept Med, Div Nephrol & Osteol, D-20246 Hamburg, Germany Univ Hamburg Hamburg Germany D-20246 & Osteol, D-20246 Hamburg, Germany Univ Penn, Sch Med, Penn Ctr Mol Studies Kidney Dis, Philadelphia, PA USA Univ Penn Philadelphia PA USA l Studies Kidney Dis, Philadelphia, PA USA Univ Penn, Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA USA Univ Penn Philadelphia PA USA lyte & Hypertens Div, Philadelphia, PA USA
Titolo Testata:
DIABETOLOGIA
fascicolo: 12, volume: 42, anno: 1999,
pagine: 1425 - 1432
SICI:
0012-186X(199912)42:12<1425:ACITRG>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; MURINE MESANGIAL CELLS; PROXIMAL TUBULAR CELLS; II-INDUCED HYPERTROPHY; HIGH GLUCOSE; TGF-BETA; RENAL HYPERTROPHY; GENE-EXPRESSION; KIDNEY-DISEASE; NEPHROPATHY;
Keywords:
diabetic nephropathy; cyclin-dependent kinase inhibitors; glomerular hypertrophy; cell cycle arrest; angiotensin II; progression of renal failure;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Wolf, G Univ Hamburg, Hosp Eppendorf, Dept Med, Div Nephrol & Osteol, Martinistr 52,Pavil 61, D-20246 Hamburg, Germany Univ Hamburg Martinistr 52,Pavil 61 Hamburg Germany D-20246 rmany
Citazione:
G. Wolf et al., "Angiotensin converting-enzyme inhibitor treatment reduces glomerular p16(INK4) and p27(Kip1) expression in diabetic BBdp rats", DIABETOLOG, 42(12), 1999, pp. 1425-1432

Abstract

Aims/hypothesis. Renal hypertrophy occurs early in diabetes mellitus and precedes the development of glomerulosclerosis and tubulointerstitial fibrosis. We have previously shown that cultured mesangial cells exposed to high glucose are arrested in the G(1)-phase of the cell cycle and undergo cellular hypertrophy. High glucose-mediated induction of p27(Kip1), an inhibitor of cyclin-dependent kinases, is essential in this process. Further investigations have also shown that p27(Kip1) and p21(Cip1), other cyclin-dependentkinase inhibitors, are up regulated in the kidneys of mice with Type I (insulin-dependent) as well as Type II (non-insulin-dependent) diabetes mellitus. Our study was undertaken to test a potential effect of short-term treatment with the angiotensin-converting enzyme inhibitor enalapril on the glomerular expression of the cyclin-dependent kinase inhibitors p16(INK4), p21(Cip1) and p27(Kip1) in BBdp rats, an autoimmune model of Type I diabetes. Methods. We evaluated p16(INK4), p21(Cip1), and p27(Kip1) protein expression in isolated glomeruli by western blots. We also assessed p27(Kip1) positive glomerular cells by immunohistochemistry. Results. Glomerular expression of all three cyclin-dependent kinase inhibitors were stimulated in BBdp rats compared with non-diabetic BBdr animals. Enalapril treatment for 3 weeks, started after the onset of diabetes, reduced the glomerular expression of p16(INK4) and p27(Kip1) but not of p21(Cip1). Enalapril also prevented the increase in kidney weights observed in BBdprats but had no effect on systolic blood pressure or glucose concentrations. Conclusion/interpretation. Our data show that enalapril attenuates the glomerular expression of cyclin-dependent kinase inhibitors in diabetes and suggest a molecular mechanism of how angiotensin-converting enzyme inhibitorsprevent renal hypertrophy in diabetes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/06/20 alle ore 23:31:10