Podocyte number predicts progression of proteinuria in IgA nephropathy.

Podocyte injury is a feature of glomerulopathies associated with proteinuria, which in turn has been used as a clinical prognostic factor for glomerular diseases. The goal of this study is to investigate the relationship between podocyte injury found in biopsied renal tissue and change of proteinuria in IgA nephropathy (IgAN). In all, 35 patients with biopsy-proven IgAN and proteinuria (>1.0 g per 24 h) were enrolled in the IgAN group, while 8 patients with excision of renal harmatoma or carcinoma served as kidney controls (Control). Immunohistochemistry was applied to detect the expression of nestin, cell-cycle regulatory protein p27, as well as complement C5b-9 and complement receptor 1 (CR1). Podocyte foot process width (FPW) and podocyte population in renal biopsied samples were measured by morphometric analysis. On the basis of the podocyte density (Nv), the IgAN patients were divided into podocytopenic group (n=17, Nv<57.10 /microm(3) x 10(6)) and normopodocytic group (n=18, Nv> or =57.10 /microm(3) x 10(6)). Changes of proteinuria were followed for 18 months after biopsy. Compared with the Control, IgAN glomeruli had reduced podocyte expression of p27 and nestin along with decreased podocyte number. IgAN glomeruli also showed activation of C5b-9 in mesangial and subepithelial areas with decreased CR1 expression in podocytes. The C5b-9 positivity was inversely correlated with the number of WT-1-positive podocytes. Although the magnitude of proteinuria at biopsy correlated with podocyte FPW (P<0.05), the change in the amount of proteinuria expressed as proteinuria progression rate significantly correlated with the podocyte density. Thus, the normopodocytic group showed significantly lower proteinuria progression rate than the podocytopenic group regardless the comparable clinical features at biopsy and treatment regimen between the two groups. The results of this study indicate that, in IgAN, podocyte injury is involved in development of proteinuria and loss of podocytes predicts progression of the proteinuria. Complement activation may contribute to podocyte damage in IgAN.

Prevention of early liver injury by breviscapine in streptozotocin-induced diabetic rats.

The aim of this study was to investigate the protective effect of breviscapine extracted from the Chinese herb Erigeron breviscapus on liver injury in diabetic rats induced by streptozotocin. Treatment with breviscapine significantly reduced liver weight, liver lipid level, fatty liver and liver fibrosis score in diabetic rats. Treatment with breviscapine also significantly decreased lipid peroxidation malondiadehyde levels and increased the activities of antioxidative enzymes such as superoxide dismutase, catalase and glutathione peroxidase in diabetic liver. Immunohistochemical observations revealed that macrophage (ED-1-positive cells) infiltration in diabetic liver was inhibited by treatment with breviscapine. Western blot analysis showed that the expression of transforming growth factor-beta1 in diabetic liver was lowered by breviscapine treatment. In conclusion, our results indicate that breviscapine has potential as a treatment for diabetic liver injury through attenuating liver lipid accumulation and oxidative stress.

Prevention of early renal injury by mycophenolate mofetil and its mechanism in experimental diabetes.

Previously it was shown that treatment with mycophenolate mofetil (MMF) attenuated renal inflammation and glomerular injury in a model of diabetes. However, the mechanism involved in the renoprotective effects of MMF in experimental diabetes has not been clearly delineated. Diabetes was induced by injection of streptozotocin (STZ) after uninephrectomy. Diabetic animals received no treatment or treatment with MMF (10 mg/kg once daily by gastric gavage) for 8 weeks, non-diabetic rats served as controls. Level of malondialdehyde (MDA) in renal tissue and urine as well as the activity of antioxidant enzymes (AOE) in renal tissue was determined. Renal injury was evaluated. Immunohistochemistry for ED-1 macrophages marker, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) was performed. Expression of transforming growth factor (TGF)-beta1 protein was determined by Western blotting analysis. Treatment with MMF had no effect on blood glucose level, but did prevent increased urinary albumin excretion and glomerular damage in diabetic rats. Oxidative stress was reduced by MMF treatment, as indicated by a reduction in MDA level in renal tissue and urine. Activity of AOE such as glutathione peroxidase (GSH-PX) was markedly elevated while superoxide dismutase (SOD) and catalase (CAT) were not changed by MMF treatment. In diabetic animals receiving no treatment, there were increases in ED-1-positive cells, ICAM-1 expression and MCP-1 expression in glomeruli and tubulointerstitium, which were effectively suppressed by MMF treatment. Western blotting analysis showed that the expression of TGF-beta1 protein was increased by 1.92-fold in renal tissue in diabetic rats, and MMF treatment significantly reduced the increased expression of TGF-beta1 protein by 45%. Our data suggest that MMF treatment ameliorates early renal injury via the inhibition of oxidative stress and overexpression of ICAM-1, MCP-1 and TGF-beta1 in renal tissue in diabetic rats.