Interferon-gamma inhibits experimental renal fibrosis.

Autor:	Oldroyd SD; Division of Clinical Sciences NGH, Sheffield Kidney Institute, University of Sheffield, Northern General Hospital, England, United Kingdom. s.d.oldroyd@sheffield.ac.uk, Thomas GL, Gabbiani G, El Nahas AM
Jazyk:	angličtina
Zdroj:	Kidney international [Kidney Int] 1999 Dec; Vol. 56 (6), pp. 2116-27.
DOI:	10.1046/j.1523-1755.1999.00775.x
Abstrakt:	Unlabelled: Interferon-gamma inhibits experimental renal fibrosis. Background: Recent evidence has implicated myofibroblasts as a cell type responsible for the laying down of extracellular matrix components during fibrosis in a number of organs. In this study, we examined the capacity of interferon-gamma (IFN-gamma) to inhibit the activation of fibroblasts to the myofibroblastic phenotype and hence reduce the extent of renal scarring in the rat subtotal nephrectomy (SNx) model using a novel method of intrarenal delivery. Methods: Rats were divided into four groups: sham, SNx (group 1), SNx + drug vehicle (group 2) and SNx + IFN-gamma (400 units/day; group 3) for 30 days. Rats were sacrificed on days 15, 30, 45, and 90 following SNx. Results: Clinical data showed a marked reduction in proteinuria in the group treated with IFN-gamma (161 vs. 280 mg/24 hr by day 45, P < 0.01) and a preservation of the creatinine clearance (1.16 vs. 0. 84 ml/min by day 45, P < 0.05) when compared to the SNx or SNx + vehicle groups throughout the time course. Immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) revealed a reduction in myofibroblastic cell types (6.5 +/- 3.1% glomerular alpha-SMA in group 3 compared with 14.8 +/- 4.2% glomerular alpha-SMA in group 2, P < 0.05, 3.8 +/- 1.4% tubulointerstitial alpha-SMA in group 3 compared with 8.8 +/- 2.0% tubulointerstitial alpha-SMA in group 2 on day 45, P < 0.05). There was also a reduction in immunostaining for collagens III and IV in the IFN-gamma-treated group. Scoring for both glomerulosclerosis and tubulointerstitial fibrosis in the IFN-gamma group (group 3) was lower than the other two operated groups. Conclusions: We conclude that IFN-gamma, administered at a dose of 400 units/day, has a strong inhibitory effect on myofibroblasts and that as a possible result of this action, renal fibrosis is reduced and renal function is preserved in the rat SNx model. The IFN-gamma renoprotective effect lasted only for the extent of its administration and subsided when discontinued.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu