Background: Hepatocyte growth factor (HGF) is a potent antifibrotic cytokine that prevents the initiation and progression of chronic renal fibrosis and inhibits transforming growth factor (TGF-beta1) expression in various animal models. Objectives: To evaluate HGF and TGF-beta1 expression in renal specimens of patients with lupus nephritis and their correlation with activity and cronicity indexes and clinical or immunological parameters. Methods: Immunohistochemical expression of HGF and TGF-beta1 was examined in tissue samples of kidneys from 28 SLE patients with nephritis (23 F, 5 M; mean ± SD age at renal biopsy 34.2 ± 11.7; mean disease duration 4.1 ± 4.4; number of class II WHO nephritis = 2; class III WHO = 2; class IV WHO = 19; class V WHO = 5; mean activity index 7.9 ± 3.6 and cronicity index 2.7 ± 2.4) and the results were evaluated following the Mizuno score (1). Activity and cronicity indexes were also determined (2) and clinical parameters were collected at the moment of the renal sample. Results: Immunohistology showed that HGF and TGF-beta1 are expressed in the tubuli but not in the glomeruli. An inverse correlation was seen between HGF and TGF-beta1 tubular expression (r=-0.82; p<0.0001), between HGF and activity index (r=-0.38; p=0.048), between HGF and cronicity index (r=-0.54, p=0.0033), while a direct correlation was observed between TGF-beta1 and cronicity index (r=0.58; p=0.0014). We did not find correlations with clinical parameters of renal involvement (proteinuria, creatinine clearance) as well as serum complement levels and anti-DNA antibodies. In three patients renal biopsy was performed after two years of cyclosporine treatment; in these patients we noted an increase of TGF-beta1 expression compared to the basal level (mean ± SD HGF score at baseline 2.7 ± 1.5 and after two years 2.7 ± 0.6; mean ± SD TGF score at baseline 2.0 ± 1.0 and after two years 2.7 ± 0.6). Conclusion: Our findings reveal that the fibrotic/antifibrotic balance may play a role in the renal damage of lupus nephritis. HGF seems to be crucially involved in determining the extent of the cronicity at the first biopsy. In particular it shuts down the expression of TGF-beta1 which might become the determinant of long-term renal failure. References: 1. Mizuno S et al. Kidney Int 2001; 59: 1304-14. 2. Austin HA 3rd et al. Kidney Int 1984; 25: 689-95.
Balance between hepatocyte growth factor (HGF) and transforming growth factor (TGF-BETA1) in renal biopsies of patients with lupus nephritis
Gremese E;
2005-01-01
Abstract
Background: Hepatocyte growth factor (HGF) is a potent antifibrotic cytokine that prevents the initiation and progression of chronic renal fibrosis and inhibits transforming growth factor (TGF-beta1) expression in various animal models. Objectives: To evaluate HGF and TGF-beta1 expression in renal specimens of patients with lupus nephritis and their correlation with activity and cronicity indexes and clinical or immunological parameters. Methods: Immunohistochemical expression of HGF and TGF-beta1 was examined in tissue samples of kidneys from 28 SLE patients with nephritis (23 F, 5 M; mean ± SD age at renal biopsy 34.2 ± 11.7; mean disease duration 4.1 ± 4.4; number of class II WHO nephritis = 2; class III WHO = 2; class IV WHO = 19; class V WHO = 5; mean activity index 7.9 ± 3.6 and cronicity index 2.7 ± 2.4) and the results were evaluated following the Mizuno score (1). Activity and cronicity indexes were also determined (2) and clinical parameters were collected at the moment of the renal sample. Results: Immunohistology showed that HGF and TGF-beta1 are expressed in the tubuli but not in the glomeruli. An inverse correlation was seen between HGF and TGF-beta1 tubular expression (r=-0.82; p<0.0001), between HGF and activity index (r=-0.38; p=0.048), between HGF and cronicity index (r=-0.54, p=0.0033), while a direct correlation was observed between TGF-beta1 and cronicity index (r=0.58; p=0.0014). We did not find correlations with clinical parameters of renal involvement (proteinuria, creatinine clearance) as well as serum complement levels and anti-DNA antibodies. In three patients renal biopsy was performed after two years of cyclosporine treatment; in these patients we noted an increase of TGF-beta1 expression compared to the basal level (mean ± SD HGF score at baseline 2.7 ± 1.5 and after two years 2.7 ± 0.6; mean ± SD TGF score at baseline 2.0 ± 1.0 and after two years 2.7 ± 0.6). Conclusion: Our findings reveal that the fibrotic/antifibrotic balance may play a role in the renal damage of lupus nephritis. HGF seems to be crucially involved in determining the extent of the cronicity at the first biopsy. In particular it shuts down the expression of TGF-beta1 which might become the determinant of long-term renal failure. References: 1. Mizuno S et al. Kidney Int 2001; 59: 1304-14. 2. Austin HA 3rd et al. Kidney Int 1984; 25: 689-95.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
