Emerging evidence suggests that transforming growth factor-␤ (TGF-␤) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-␤ antibody (␣T) 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 ␣T prevents renal insufficiency and glomerulosclerosis in the db͞db mouse, a model of type 2 diabetes that develops overt nephropathy. Diabetic db͞db mice and nondiabetic db͞m littermates were treated intraperitoneally with ␣T or control IgG, 300 g three times per week for 8 wk. Treatment with ␣T, but not with IgG, significantly decreased the plasma TGF-␤1 concentration without decreasing the plasma glucose concentration. The IgG-treated db͞db 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 db͞db 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-␤ with a neutralizing monoclonal antibody in db͞db mice prevents the glomerulosclerosis and renal insufficiency resulting from type 2 diabetes.

The diagnostic accuracy of the new EUS-TNB is comparable to that of EUS-FNA. In our experience, the overall efficacy and safety profile of the Trucut needle appears modest.

No abstract

High glucose stimulates total TGF-beta1 protein production and bioactivity as well as the steady-state level of TGF-beta1 mRNA. The latter effect is due primarily to stimulation of gene transcription rate rather than message stability. Transcriptional activation by high glucose may involve a region in the TGF-beta1 promoter containing a putative glucose-response element.