The transforming growth factor beta system in kidney disease and repair: recent progress and future directions

Transforming growth factor beta is a multifunctional polypeptide growth fac tor implicated in a variety of renal diseases. The expression of transformi ng growth factor beta is enhanced in renal diseases and available evidence suggests that its activity in promoting the synthesis of extracellular matr ix plays a crucial role in fibrotic deposition and the decline in renal fun ction. Transforming growth factor beta is, however, also expressed in respo nse to renal injury and may play an important role in normal repair process es. It appears that renal diseases may result from the inappropriate regula tion of transforming growth factor beta expression. The determination of th e factors that mediate transforming growth factor beta activity will be of primary importance in elucidating the mechanisms leading to renal disease o r repair after injury. Both in-vitro and in-vivo studies have demonstrated that proteolytic activity, thrombospondin-l, elevated glucose, angiotensin II, oxidant stress and hemodynamic forces regulate transforming growth fact or beta activity through both transcriptional and post-transcriptional mech anisms. In some cases, therapies that may partly disrupt renal transforming growth factor beta activity have shown promise in slowing the progression to end-stage renal disease. Curr Opin Nephrol Hypertens 8:21-30. (C) 1999 L ippincott Williams & Wilkins.