Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-β antibody indb/dbdiabetic mice

• DOI: 10.1073/pnas.120055097
• Publication Date: 2002-07-26T14:37:36Z
• Authors: Fuad N. Ziyadeh; Brenda B. Hoffman; Dong Cheol Han; M. Carmen Iglesia...; Soon Won Hong; Motohide Isono; Sheldon Chen; Tracy A. McGowan; Kumar Sharma
• Keywords: Glomerulosclerosis; Albuminuria; Renal Hypertrophy

Emerging evidence suggests that transforming growth factor-β (TGF-β) is an important mediator of diabetic nephropathy. We showed previously short-term treatment with a neutralizing monoclonal anti-TGF-β antibody (αT) in streptozotocin-diabetic mice prevents early changes renal hypertrophy and increased matrix mRNA. To establish overactivity the TGF-β system mediates functional structural more advanced stages nephropathy, we tested whether chronic administration αT insufficiency glomerulosclerosis db/db mouse, model type 2 diabetes develops overt Diabetic nondiabetic db/m littermates were treated intraperitoneally or control IgG, 300 μg three times per week for 8 wk. Treatment αT, but not significantly decreased plasma TGF-β1 concentration without decreasing glucose concentration. The IgG-treated developed albuminuria, insufficiency, glomerular mesangial expansion associated mRNAs encoding α1(IV) collagen fibronectin. On other hand, completely prevented increase creatinine concentration, decrease urinary clearance, mice. was substantially attenuated, excretion albumin factored clearance affected by treatment. conclude inhibition biologic actions resulting from diabetes.