Role of angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats

Objective:To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. Methodology:Seventy male Wistar rats were randomly allocated into control group (control, n=30) and daunorubicin group (DRB,n=40). The rats in DRB group were injected into rats' tail with DRB (15 mg/kg). Since then, at week 1, 2, 4, 6, 8 and 12 respectively, 5 rats in each group were taken randomly for determining the level of 24hr urinary protein excretion (UPE), plasma TNF-α, angiopoietin-1(Ang1), and angiopoietin-2(Ang2). The renal histological examinations were used by PAS staining, immunohistochemical staining, in situ hybridization histochemistry methods and electric microscope. Results:With progression of glomerulosclerosis, the expression of Ang 1 mRNA and protein in glomeruli decreased, while the expression of TNF-α protein, Ang 2 mRNA and proteinin glomeruli increased in rats with DRB treated. The expression of Ang 1 mRNA and protein in glomeruli had a negative correlation with UPE. The level of plasma Ang 2, expression of Ang 2 mRNA and protein in glomeruli had a positive correlation with UPE. The level of plasma TNF-α and TNF-α expression in glomeruli had a positive correlation with the expression of Ang 2 mRNA and protein in glomeruli. In glomeruli, the expression of Ang1 protein had a negative correlation with the expression of Ang 2, while the expression of Ang2 protein had a positive correlation with the expression of Fn protein and MAECM. Conclusion:In daunorubicin-induced progressive glomerulosclerosis, the expression of Ang1 downregulated and the expression of Ang2 upregulated in glomeruli. An increase in plasma level and in glomerular expression of Ang 2 may mediate an increase in permeability of the glomerular filtration barrier. In adition, Ang 2 may upregulate the expression of component of extracellular matrix to contribute to glomerulosclerosis.