In DN, hyperglycemia causes increase in the expression of TGF- β genes, TGF- β proteins and their receptors. Increased glucose level mediates these effects through activation of polyol pathway, protein kinase C pathway, hexosamine pathway, increases advanced glycation end products (AGE) and increases oxidative stress. Hyperglycemia also activates the TGF- β via activation of glucose transporters (GLUT), angiotensine II and platelet derived growth factor (PDGF). Activated TGF-β further leads to glomerular basement membrane (GBM) thickening and glomerulosclerosis through activation of connective tissue growth factor (CDGF) and vascular endothelial growth factor (VEGF).
We have discussed the progression of hyperglycemia to DN via TGF- β, whose schematic presentation may serve as an effective way to understand the mechanisms and to find out an effective way for the management of diabetic nephropathy.