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Titolo:
Effects of glucose dialysate on extracellular matrix production by human peritoneal mesothelial cells (HPMC): the role of TGF-beta
Autore:
Medcalf, JF; Walls, J; Pawluczyk, IZA; Harris, KPG;
Indirizzi:
Leicester Gen Hosp, Dept Nephrol, Leicester LE5 4PW, Leics, England Leicester Gen Hosp Leicester Leics England LE5 4PW E5 4PW, Leics, England
Titolo Testata:
NEPHROLOGY DIALYSIS TRANSPLANTATION
fascicolo: 9, volume: 16, anno: 2001,
pagine: 1885 - 1892
SICI:
0931-0509(200109)16:9<1885:EOGDOE>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
MESANGIAL CELLS; TUBULAR CELLS; MESSENGER-RNA; HEMODIALYSIS; FIBRONECTIN; EXPRESSION; TGF-BETA-1; MULTICENTER; MORPHOLOGY; COLLAGEN;
Keywords:
CAPD; dialysis solutions; extracellular matrix proteins; glucose; mesothelial cells; TGF-beta;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Harris, KPG Leicester Gen Hosp, Dept Nephrol, Gwendolen Rd, Leicester LE5 4PW, Leics, England Leicester Gen Hosp Gwendolen Rd Leicester Leics EnglandLE5 4PW
Citazione:
J.F. Medcalf et al., "Effects of glucose dialysate on extracellular matrix production by human peritoneal mesothelial cells (HPMC): the role of TGF-beta", NEPH DIAL T, 16(9), 2001, pp. 1885-1892

Abstract

Background. Dialysate glucose has been implicated in the loss of peritoneal membrane function seen in long-term CAPD patients. Methods. In order to investigate this in vitro, human peritoneal mesothelial cells (HPMC) were cultured in a 50:50 mix of dialysis solution and M199 for 12 h. The dialysate was laboratory manufactured and designed to be identical in composition to PD4 (LAB). The final glucose concentration ranged between 5 and 40 mmol/l. Experiments were conducted in the presence and absence of an anti-transforming growth factor-beta (TGF-beta) antibody. Cell viability was measured by lactate dehydrogenase (LDH) release. Fibronectin (FN) and TGF-beta protein were measured by ELISA, and FN gene expression was measured by Northern analysis. Separately, the effects of recombinant TGF-beta (1) added to M199: dialysate at 5 mmol/l glucose were investigated. Results. Forty millimoles per litre D-glucose LAB caused a decrease in cell viability, as evidenced by an increase in LDH release (6.0 +/-1.3 vs 2.6 /-0.7%). This effect was dependent on osmolality. Forty millimoles per litre D-glucose LAB stimulated a 15.4 +/-4.6% increase in FN, a 46.5 +/- 18.3%increase in TGF-beta protein (both P <0.05), and 1.4 +/-0.09-fold increasein FN mRNA compared with 5 mmol/l D-glucose LAB. Exogenous TGF-beta 0-1 ng/ml induced a dose-dependent increase in FN protein (280 +/- 45% increase at TGF-beta 1 ng/ml, P <0.0001), and FN mRNA levels (10.0 +/-1.8-fold at TGF-beta 1 ng/ml). The increase in FN in response to 40 mmol/l glucose was significantly reduced by anti-TGF-beta antibody to levels not different from control (93.8 +/-6.6%, P <0.05 vs no Ab). Conclusions. These data suggest that the pro-fibrotic effect of glucose dialysate on HPMC is mediated through stimulation of TGF-beta, which promotesFN Cr gene expression and protein production.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 16:11:31