The use of transgenic animals in the study of diabetic kidney disease

Diabetic nephropathy is one of the most common diseases leading to fibrosis and end-stage renal disease (ESRD) world wide. Under normal conditions, a delicate equilibrium exists between synthesis, composition, and removal of extracellular matrix (ECM). If this is disturbed, ECM accumulation and fibrosis may result. The fragile balance between synthesis and removal of ECM is crucial for the prognosis of glomerular as well as interstitial pathological processes. Some features may favor ECM accumulation and progression to ESRD (dialysis and transplantation), whereas other elements may favor ECM removal and resolution (recovery). Pathogenetic mechanisms and the cellular sources of ECM in the glomerular basement membrane as well as in the tubulointerstitial space are still under investigation. Among several growth factors, transforming growth factor beta1 (TGF-beta1) plays a major role. We consider the use of living animals necessary for our understanding of the complex biological processes that occur during the development of ESRD. The present review will discuss the glomerular as well as interstitial accumulation of ECM and the use of transgenic animals in studying the pathogenetic mechanisms with special emphasis on diabetic kidney disease and TGF-beta1.