A potential pathological role of angiopoietins expression in glomeruli during progressive glomerulisclerosis related to podocyte injury.
A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation group (Sham, n = 25), Uninephrectomy group (UPHT, n = 25) and Uninephrectomy+Daunorubicin group (DRB, n = 30). In DRB group, daunorubicin (5 mg/kg) was injected via tail vein on the 7th and 14th day after uninephrectomy. At week 1, 2, 4, 6 and 8 respectively following establishment of the animal model, 5 rats in Sham group and UPHT group, and 6 in DRB group were taken respectively for determining 24-h urinary protein excretion rate (24hUPER), blood urea nitrogen (BUN) and serum creatinine (Scr). The sections of kidneys were examined by an electric microscope, PAS staining, immunohistochemical staining and in situ hybridization histochemistry. The results showed that 24hUPER, BUN and Scr in DRB group were more than those in Sham group and UPHT group at the same time points, and there was a trend towards an increase on level of GSI in DRB group from week 2 to week 8. Electric microscopy revealed that podocyte injury presented in DRB group. The expression of Ang1 mRNA and protein in glomeruli of DRB group was decreased, while the expression of Ang2 protein in glomeruli of DRB group increased. Meanwhile, the expression of Ang1 mRNA had a negative correlation with the expression of Ang2 mRNA, and the expression of Ang1 protein had a positive correlation with the expression of Ang1 mRNA, and had a negative correlation with 24hUPER, BUN, Scr, glomerular sclerotic index (GSI), the expression of Ang2 protein and CoIV protein. The expression of Ang2 protein had a positive correlation with the expression of Ang2 mRNA, and had a positive correlation with 24hUPER, BUN, Scr, GSI, the expression of CoIV protein. It was concluded that podocyte injury might lead to an alteration in the expression of Ang1 and Ang2 within glomeruli. Ang2 may get rid of inhibition from Ang1 for downregulation of the Ang1 expression, which facilitate upregulation of the Ang2 expression in glomeruli to promote progressive glomerulosclerosis in the rats.
Lu
Yuanhang
Y
Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Deng
Anguo
A
Yang
Xiao
X
Liu
Jianshe
J
Zhu
Zhonghua
Z
D042683:Angiopoietin-1 / Q000096:biosynthesis* / Q000235:genetics; D042702:Angiopoietin-2 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D003630:Daunorubicin / Q000031:analogs & derivatives; D018450:Disease Progression; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009392:Nephrectomy; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D012333:RNA, Messenger; C000847:daunorubicinol; D003630:Daunorubicin