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Titolo:
Molecular mechanisms of diabetic renal hypertrophy
Autore:
Wolf, G; Ziyadeh, FN;
Indirizzi:
Univ Penn, Penn Ctr Mol Studies Kidney Dis, Dept Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Dept Med, Philadelphia, PA 19104 USA Univ Hamburg, Dept Med, Div Nephrol & Osteol, Hamburg, Germany Univ Hamburg Hamburg Germany ed, Div Nephrol & Osteol, Hamburg, Germany Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 rtens Div, Philadelphia, PA 19104 USA
Titolo Testata:
KIDNEY INTERNATIONAL
fascicolo: 2, volume: 56, anno: 1999,
pagine: 393 - 405
SICI:
0085-2538(199908)56:2<393:MMODRH>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; GLOMERULAR MESANGIAL CELLS; PROTEIN-KINASE-C; PROXIMAL TUBULAR CELLS; ORNITHINE DECARBOXYLASE ACTIVITY; THROMBOXANE-INDUCED INCREASES; HIGH GLUCOSE-CONCENTRATIONS; II-INDUCED HYPERTROPHY; RECEPTOR-A ANTAGONIST; ANGIOTENSIN-II;
Keywords:
diabetes mellitus; glomerulopathy; angiotensin; TGF-beta; cell cycle; glucose; cyclin;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
153
Recensione:
Indirizzi per estratti:
Indirizzo: Ziyadeh, FN Univ Penn, Renal Electrolyte & Hypertens Div, 700 Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA Univ Penn 700 Clin Res Bldg,415 Curie Blvd Philadelphia PA USA 19104
Citazione:
G. Wolf e F.N. Ziyadeh, "Molecular mechanisms of diabetic renal hypertrophy", KIDNEY INT, 56(2), 1999, pp. 393-405

Abstract

Altered growth of renal cells is one of the early abnormalities detected after the onset of diabetes. Cell culture studies whereby renal cells are exposed to high glucose concentrations have provided a considerable amount ofinsight into mechanisms of growth. In the glomerular compartment, there isa very early and self-limited proliferation of mesangial cells with subsequent hypertrophy, whereas proximal tubular cells primarily undergo hypertrophy. There is overwhelming evidence from in vivo and cell culture studies that induction of the transforming growth factor-beta (TGF-beta) system mediates the actions of high ambient glucose and that this system is pivotal for the hypertrophy of mesangial and tubular cells. Other factors such as hemodynamic forces, protein glycation products, and several mediators (for example, angiotensin II, endothelin-l, thromboxane, and platelet-derived growth factor) may further amplify the synthesis of TGF-beta and/or the expression of its receptors in the diabetic state. Cellular hypertrophy can be characterized by cell cycle arrest in the G(1) phase. The molecular mechanism arresting mesangial cells in the G(1) phase of the cell cycle is the induction of cyclin-dependent kinase (CdK) inhibitors such as p27(Kip1) and p21, which bind to and inactivate cyclin-CdK complexes responsible for G(1)-phaseexit. High-glucose-induced activation of protein kinase C and stimulated TGF-beta expression appear to be essential for stimulated expression of p27(Kip1). I, addition, a decreased turnover of protein caused by the inhibition of proteases contributes to hypertrophy. The development of irreversible renal changes in diabetes mellitus such as glomerulosclerosis and tubulointerstitial fibrosis is always preceded by the early hypertrophic processes in the glomerular and the tubular compartments. It may still be debated whether diabetic renal hypertrophy will inevitably lead to irreversible fibrotic changes in the absence of other factors such as altered intraglomerular hemodynamics and genetic predisposition. Nevertheless, understanding cellular growth on a molecular level may help design a novel therapeutic approach to prevent or treat diabetic nephropathy effectively.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 09:44:06