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- Title
Interferon-γ inhibits experimental renal fibrosis.
- Authors
Oldroyd, Simon D.; Thomas, Graham L.; Gabbiani, Giulio; El Nahas, A. Meguid
- Abstract
Interferon-γ 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-γ (IFN-γ) 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-γ (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-γ (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 α-smooth muscle actin (α-SMA) revealed a reduction in myofibroblastic cell types (6.5 ± 3.1% glomerular α-SMA in group 3 compared with 14.8 ± 4.2% glomerular α-SMA in group 2, P < 0.05, 3.8 ± 1.4% tubulointerstitial α-SMA in group 3 compared with 8.8 ± 2.0% tubulointerstitial α-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-γ–treated group. Scoring for both glomerulosclerosis and tubulointerstitial fibrosis in the IFN-γ group (group 3) was lower than the other two operated groups. Conclusions. We conclude that IFN-γ, 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-γ renoprotective...
- Subjects
INTERFERONS; KIDNEY diseases; PHYSIOLOGY
- Publication
Kidney International, 1999, Vol 56, Issue 6, p2116
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.1999.00775.x