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Titolo:
Monocyte-mesangial cell interactions in high-glucose co-cultures
Autore:
Mene, P; Caenazzo, C; Pugliese, F; Cinotti, GA; DAngelo, A; Garbisa, S; Gambaro, G;
Indirizzi:
Univ La Sapienza, Div Nephrol, Dept Clin Sci, Rome, Italy Univ La Sapienza Rome Italy za, Div Nephrol, Dept Clin Sci, Rome, Italy Univ Padua, Div Nephrol, Dept Med & Surg Sci, Padua, Italy Univ Padua Padua Italy , Div Nephrol, Dept Med & Surg Sci, Padua, Italy
Titolo Testata:
NEPHROLOGY DIALYSIS TRANSPLANTATION
fascicolo: 5, volume: 16, anno: 2001,
pagine: 913 - 922
SICI:
0931-0509(200105)16:5<913:MCIIHC>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; MATRIX; PROLIFERATION; MACROPHAGES; EXPRESSION; ADHESION;
Keywords:
collagen; diabetic nephropathy; matrix; mesangium; metalloproteinase; monocytes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Mene, P Policlin Umberto I, Dipartimento Sci Clin, Cattedra Nefrol, Viale Policlin155, I-00161 Rome, Italy Policlin Umberto I Viale Policlin 155 Rome Italy I-00161 e, Italy
Citazione:
P. Mene et al., "Monocyte-mesangial cell interactions in high-glucose co-cultures", NEPH DIAL T, 16(5), 2001, pp. 913-922

Abstract

Background. Monocytes bind to human mesangial cells (HMC) in a co-culture model of leukocyte/glomerular cell interactions. Since monocytic infiltration has been demonstrated in the early stages of diabetic glomerulopathy, weexamined whether co-culture with myelomonocytes of the U937 cell line in media mimicking the diabetic microenvironment modulated phenotype, growth, and extracellular matrix production patterns of HMC. Methods. HMC monolayers grown for 5 daps in 5.5 mmol/l (NG) or 30 mmol/l (HG) glucose media were examined 3, 24 and 48 h after addition of U937 cellsby computer-assisted image analysis/fluorescence microscopy following fixation, staining for cell adhesion, and TUNEL/propidium iodide labelling for apoptosis. As matrix components may be relevant to both phenotype of cultured HMC and monocyte adhesion, reverse transcription-polymerase chain reaction. zymography, and ELISA were used to detect urokinase-plasminogen activator (uPa), collagen type IV (COL IV), transforming growth factor beta1 (TGF-beta1), matrix metalloproteinases (MMP), and relative inhibitors (tissue inhibitor of MMP (TIMP)) expression in co-cultures in NG/HG. Results. U937 adhesion at 1-3 h was increased in HG (from 54.9 +/- 6.6 to 87.1 +/- 5.8% U937/HMC). Control HMC proliferating in NG supplemented with 10% fetal bovine serum had an average cross-sectional area of 9993 +/- 505 mu (2) with 1.2 +/- 0.1 hillocks/high-power field, which increased to 13 651 +/- 1114 mu (2) with 0.5 +/- 0.2 hillocks/high-power field in HG (P < 0.05). TUNEL + HMC were nearly identical (4.9 <plus/minus> 1.7 vs 4.2 +/- 0.4%in HG, P = NS). Enhanced transcription and secretion of urokinase (uPA, +656%), COL IV (+137%), TGF-beta1 (+590%) were observed in co-cultures in HG. COL IV and TGF-beta1, but not uPA, were also increased in HMC alone, exposed to HG for 5 days, MMP-2/TIMP-2 ratio was decreased while MMP-1/TIMP-1 was increased in KG co-cultures. In both NG and HG, U937 adhesion reduced HMCnumber and hillocks at 24 h, with constant apoptosis. The effects of U937 were no longer detectable at 48 h, when apoptosis was 2.1 +/- 0.6 vs 4.0 +/- 0.4% in HG, and cell counts returned above basal, possibly due to a delayed proliferative response. Conclusions. High glucose medium increases U937 cell adhesion to HMC. In turn, monocytes modulate number and spatial distribution of HMC, which are also markedly affected by ambient glucose levels. These interactions may be relevant to leukocyte infiltration, mesangial expansion, and glomerulosclerosis in diabetes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 11:55:17