title: Hyperglycemia to nephropathy via transforming growth factor beta.
abstract: Nephropathy is one of the major complications of diabetes which further directs to end stage renal disease. Extensive work has been done to find out the mechanisms involved in pathogenesis of the DN. Now, many researchers have been convinced that almost all of the molecular mediators and intracellular signaling pathways involved in progression of diabetic nephropathy have involvement in transforming growth factor beta (TGF- β) at some stage. 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.
authors.forename: Mayuresh Sudamrao
authors.initials: MS
authors.lastname: Garud
authors.affiliation: SPP School of Pharmacy & Technology Management, SVKM's NMIMS, Mumbai-56, India. yogeshkulkarni101@yahoo.com.
authors.forename: Yogesh Anant
authors.initials: YA
authors.lastname: Kulkarni
mesh_terms: D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology*; D018450:Disease Progression; D051296:Glucose Transporter Type 5 / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051296:Glucose Transporter Type 5; D017127:Glycation End Products, Advanced; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C