Atorvastatin inhibits hyperglycemia-induced expression of osteopontin in the diabetic rat kidney via the p38 MAPK pathway.
Osteopontin (OPN), a large phosphoglycoprotein adhesion molecule, which is up-regulated in the kidneys of humans and mice with diabetes, has emerged as a potentially key pathophysiological contributor in diabetic nephropathy. Here, we investigated the role of OPN in kidney injury caused by diabetic nephropathy and the effect of atorvastatin on the expression of OPN and on diabetic nephropathy. Diabetes was induced with streptozotocin in rats, and atorvastatin (5 mg/kg) was orally administered once a day for 8 weeks. We analyzed the expression and regulation of OPN in the kidneys of streptozotocin-induced diabetic Sprague-Dawley albino rats by immunohistochemistry and western blot analysis. The expression of OPN was increased in diabetic rat kidney, and atorvastatin inhibited this process. Atorvastatin also decreased the expression and phosphorylation of p38. In vitro, atorvastatin inhibited the high glucose-induced OPN expression in Madin-Darby canine kidney epithelial cells through the p38 MAPK signaling pathway. These results suggested that atorvastatin reduced the expression of OPN through inhibition of the p38 MAPK pathway. The expression of OPN was associated with kidney injury. These molecules may represent therapeutic targets for the prevention of acute kidney injury induced by diabetes.
Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.
Li
L
Zuo
Yong
Y
Du
Man
M
Lu
Junling
J
Gao
Ruolei
R
Hu
Sumei
S
Zhang
Yi
Y
Wang
Huaqing
H
Zhu
Qing
Q
Zhou
Wei
W
Wei
Yuan
Y
Wang
D000818:Animals; D000069059:Atorvastatin; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006943:Hyperglycemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D001786:Blood Glucose; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D053495:Osteopontin; D000069059:Atorvastatin; D048051:p38 Mitogen-Activated Protein Kinases