Progression of diabetic nephropathy

被引:164
作者
Kikkawa, R [1 ]
Koya, D [1 ]
Haneda, M [1 ]
机构
[1] Shiga Univ Med Sci, Dept Med 3, Shiga 5202192, Japan
关键词
diabetic nephropathy; protein kinase C (PKC); mitogen-activated protein kinase (MAPK); mechanical stretch; protein kinase C (PKC) beta inhibitor;
D O I
10.1053/ajkd.2003.50077
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background: Diabetic nephropathy, a kidney disease caused by diabetes, is the most devastating and money-consuming complication in patients with diabetes throughout the world. The cardinal lesion of diabetic nephropathy resides in renal glomeruli and is called diabetic glomerulosclerosis. Hyperglycemia is responsible for the development and progression of diabetic nephropathy through metabolic derangements, including increased oxidative stress, renal polyol formation, activation of protein kinase C (PKC)-mitogen-activated protein kinases (MAPKs), and accumulation of advanced glycation end products, as well as such hemodynamic factors as systemic hypertension and increased intraglomerular pressure. Methods: We examined whether inhibition of the PKC-MAPK pathway could inhibit functional and pathological abnormalities in glomeruli from diabetic animal models and cultured mesangial cells exposed to high glucose condition and/or mechanical stretch. Results: Direct inhibition of PKC by PKC beta inhibitor prevented albuminuria and mesangial expansion in db/db mice, a model of type 2 diabetes. We also found that inhibition of MAPK by PD98059, an inhibitor of MAPK, or mitogen-activated extracellular regulated protein kinase kinase prevented enhancement of activated protein-1 (AP-1) DNA binding activity and fibronectin expression in cultured mesangial cells exposed to mechanical stretch in an in vivo model of glomerular hypertension. Conclusion: These findings highlight the important role of PKC-MAPK pathway activation in mediating the development and progression of diabetic nephropathy.
引用
收藏
页码:S19 / S21
页数:3
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