Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis  

作　　者：Yuan-hang LU An-guo DENG Ning LI Ming-na SONG Xiao YANG Jian-she LIU 

机构地区：[1]Department of Nephrology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China [2]School of Pharmacy, University of Louisiana, 700 University Avenue, Monroe, LA 71209 USA [3]Morton Grove Pharmaceuticals, Inc 50 LakeviewParkway, suite 127Vernon Hills, Illinois 60061, USA

出　　处：《Acta Pharmacologica Sinica》2006年第5期579-587,共9页中国药理学报（英文版）

基　　金：Project supported by the Hi-Tech Research Program of the Committee of Science and Technology of Hebei Province(No 20000414).

摘　　要：Aim： To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. Methods： Seventy male Wistar rats were allocated randomly into a daunorubicin group （DRB; n=40） or a control group （n=30）. The rats in the DRB group were injected with DRB （15 mg/kg）, in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements （24 h UPQM）, and determination of plasma tumor necrosis factor α （TNF-α）, angiopoietin-1 （Ang 1）, and angiopoietin-2 （Ang2） levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff （PAS） staining, immunohistochemical staining and in situ hybridization histochemistry. Results： As glomerulosclerosis progressed in the DRB group, expression of Angl mRNA and protein in glomeruli decreased and expression of TNF-α protein, Ang2 mRNA and protein in glomeruli increased. Expression ofAngl mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix （MAECM）. In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-α and expression of TNF-α in glomeruli were positively correlated with expression ofAng2 mRNA and protein in glomeruli. There was a negative correlation between Angl protein expression and Ang2 protein expression in glomeruli. Conclusion： During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Angl and Ang2 in glomeruli. Increased TNF-α in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate thAim： To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. Methods： Seventy male Wistar rats were allocated randomly into a daunorubicin group （DRB; n=40） or a control group （n=30）. The rats in the DRB group were injected with DRB （15 mg/kg）, in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements （24 h UPQM）, and determination of plasma tumor necrosis factor α （TNF-α）, angiopoietin-1 （Ang 1）, and angiopoietin-2 （Ang2） levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff （PAS） staining, immunohistochemical staining and in situ hybridization histochemistry. Results： As glomerulosclerosis progressed in the DRB group, expression of Angl mRNA and protein in glomeruli decreased and expression of TNF-α protein, Ang2 mRNA and protein in glomeruli increased. Expression ofAngl mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix （MAECM）. In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-α and expression of TNF-α in glomeruli were positively correlated with expression ofAng2 mRNA and protein in glomeruli. There was a negative correlation between Angl protein expression and Ang2 protein expression in glomeruli. Conclusion： During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Angl and Ang2 in glomeruli. Increased TNF-α in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate th

关 键 词：ANGIOPOIETINS GLOMERULOSCLEROSIS DAUNORUBICIN podocyte 

分 类 号：R692[医药卫生—泌尿科学]