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Long-Term Prevention Of Renal Insufficiency, Excess Matrix Gene Expression, And Glomerular Mesangial Matrix Expansion By Treatment With Monoclonal Antitransforming Growth Factor-Ss Antibody In Db/Db Diabetic Mice , Fuad N. Ziyadeh, Brenda B. Hoffman, Dong Cheol Han, M. Carmen Iglesias-De La Cruz, Soon Won Hong, Motohide Isono, Sheldon Chen, Tracy A. Mcgowan, Kumar Sharma

Department of Medicine Faculty Papers

Emerging evidence suggests that transforming growth factor-(TGF-β) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-antibody (αT) in streptozotocin-diabetic mice prevents early changes of renal hypertrophy and increased matrix mRNA. To establish that overactivity of the renal TGF-system mediates the functional and structural changes of the more advanced stages of nephropathy, we tested whether chronic administration of αT prevents renal insufficiency and glomerulosclerosis in the db/db mouse, model of type 2 diabetes that develops overt nephropathy. Diabetic db/db mice and nondiabetic db/m littermates were treated intraperitoneally with α or control IgG, …