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标题：Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-β antibody in db/db diabetic mice
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作者：Fuad N. Ziyadeh ; Brenda B. Hoffman ; Dong Cheol Han 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2000
卷号：97
期号：14
页码：8015-8020
DOI：10.1073/pnas.120055097
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Emerging evidence suggests that transforming growth factor-{beta} (TGF-{beta}) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-{beta} antibody (T) in streptozotocin-diabetic mice prevents early changes of renal hypertrophy and increased matrix mRNA. To establish that overactivity of the renal TGF-{beta} system mediates the functional and structural changes of the more advanced stages of nephropathy, we tested whether chronic administration of T prevents renal insufficiency and glomerulosclerosis in the db/db mouse, a model of type 2 diabetes that develops overt nephropathy. Diabetic db/db mice and nondiabetic db/m littermates were treated intraperitoneally with T or control IgG, 300 {micro}g three times per week for 8 wk. Treatment with T, but not with IgG, significantly decreased the plasma TGF-{beta}1 concentration without decreasing the plasma glucose concentration. The IgG-treated db/db mice developed albuminuria, renal insufficiency, and glomerular mesangial matrix expansion associated with increased renal mRNAs encoding 1(IV) collagen and fibronectin. On the other hand, treatment with T completely prevented the increase in plasma creatinine concentration, the decrease in urinary creatinine clearance, and the expansion of mesangial matrix in db/db mice. The increase in renal matrix mRNAs was substantially attenuated, but the excretion of urinary albumin factored for creatinine clearance was not significantly affected by T treatment. We conclude that chronic inhibition of the biologic actions of TGF-{beta} with a neutralizing monoclonal antibody in db/db mice prevents the glomerulosclerosis and renal insufficiency resulting from type 2 diabetes.