Thrombospondin 1 mediates angiotensin II induction of TGF-beta activation by cardiac and renal cells under both high and low glucose conditions.

Renal and cardiac fibrosis leading to organ failure are complications of both diabetes and hypertension. These disease processes, when combined, exacerbate development of fibrotic complications. Control of latent transforming growth factor (TGF)-beta activation is a potential determinant of fibrotic progression.

Amino acids induce indicators of response to injury in glomerular mesangial cells.

High-protein diets exacerbate glomerular hyperfiltration and the progression of diabetic nephropathy. The purpose of this study was to determine whether amino acids also produce nonhemodynamic injury in the glomerulus. When rat mesangial cells were cultured with an amino acid mixture designed to replicate the composition in plasma after protein feeding, production of mRNA (Northern blot analysis) and/or protein (ELISA or Western blot analysis) for transforming growth factor-beta1 (TGF-beta1), fibronectin, thrombospondin-1 (TSP-1), and collagen IV were enhanced in a manner comparable to a culture with high glucose (30.

Nitric oxide and cGMP-dependent protein kinase regulation of glucose-mediated thrombospondin 1-dependent transforming growth factor-beta activation in mesangial cells.

Excessive transforming growth factor-beta (TGF-beta) activity in hyperglycemia contributes to the development of diabetic nephropathy. Glucose stimulation of TGF-beta activity and matrix synthesis are dependent on autocrine thrombospondin 1 (TSP1) to convert latent TGF-beta to its biologically active form. The mechanisms by which glucose regulates TSP1 are not known.