Glomerular extracellular matrix in glomerulosclerosis by molecular biology

Many renal diseases progress to end-stage renal failure with glomerulosclerosis, irrespective of the cause of the disease. Glomerulosclerosis is characterized by an accumulation of extracellular matrices (ECM) due to increased synthesis of the ECM and/or decreased degradation of the ECM. Sclerotic lesions represent an accumulation of normal constituents of the ECM, including type IV collagen, laminin, proteoglycans, as well as, abnormal constituents such as type I and III collagens. The cDNAs for various ECM constituents have been obtained and it has become possible to study the status of their synthesis, in the transcriptional level, in various glomerular diseases. Studies suggest that hemodynamic factors and growth factors, such as, TGF-beta and PDGF are responsible for the development of glomerulosclerosis. Inappropriate expression of intrinsic mesangial cell metalloproteinases and tissue inhibitors of metalloproteinases also lead to glomerulosclerosis.