Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis.
OBJECTIVE
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 alpha (TNF-alpha), angiopoietin-1 (Ang1), 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 Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 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-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli.


CONCLUSIONS
During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha 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 the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.
Lu
Yuan-Hang
YH
Department of Nephrology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. luyuanhanglyj@tom.com
Deng
An-Guo
AG
Li
Ning
N
Song
Ming-Na
MN
Yang
Xiao
X
Liu
Jian-She
JS
D042683:Angiopoietin-1 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D042702:Angiopoietin-2 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D000818:Animals; D003630:Daunorubicin; D005353:Fibronectins / Q000097:blood / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D005353:Fibronectins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003630:Daunorubicin