Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats.
BACKGROUND
The changes in matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were examined in the kidneys of diabetic rats to investigate the degradative pathway of collagen type IV (C-IV) and the protective effects of pioglitazone on an experimental model of diabetic nephropathy.


METHODS
In 54 SD rats used in our study, 18 served as normal controls. Diabetes mellitus was induced in 36 age- and weight-matched rats by intraperitoneal injection of streptozotocin (70 mg/kg); 18 of the diabetic rats were allocated at random to receive pioglitazone [20 mg.kg(-1).d(-1)] in their drinking water and 18 served as diabetic controls. Rats were killed after 2, 4, or 8 weeks of treatment. Kidneys were examined pathomorphologically and the expressions of MMP-2, MMP-9, and C-IV were analyzed by immunohistochemistry, and the results were quantified by image analysis techniques.


RESULTS
Diabetes mellitus was associated with a decrease in the expression of MMP-2 in the glomeruli (P < 0.05, vs control). By contrast, MMP-2 expression in the interstitium increased, but not significantly (P > 0.05, vs control). The expression of MMP-9 did not show any change when comparing the three groups (P > 0.05, vs control). STZ-diabetic rats were also associated with an increase in the expression of C-IV in the glomeruli and the interstitium (P < 0.05, vs control). All diabetes-associated changes in MMP-2 expression were attenuated by pioglitazone treatment in association with reduced C-IV accumulation.


CONCLUSIONS
These results indicate that a decrease in MMP-2 expression in the glomeruli of diabetic rats may lead to impairment of C-IV degradation and contribute to the matrix accumulation in diabetic nephropathy. Pioglitazone treatment, which can attenuate the decrease of glomerular MMP-2 and the increase of C-IV degradation, has curative effects on diabetic nephropathy.
Dong
Feng-qin
FQ
Department of Endocrinology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Li
Hong
H
Cai
Wei-min
WM
Tao
Jun
J
Li
Qun
Q
Ruan
Yu
Y
Zheng
Fen-ping
FP
Zhang
Zhe
Z
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000201:enzymology; D020778:Matrix Metalloproteinase 2 / Q000032:analysis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000032:analysis* / Q000235:genetics; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D045162:Thiazolidinediones / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D045162:Thiazolidinediones; D013311:Streptozocin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077205:Pioglitazone