PDGF and the progression of renal disease

Abstract

Progressive renal diseases represent a global medical problem, in part because we currently lack effective treatment strategies. Inhibition of platelet-derived growth factors (PDGFs) might represent one such novel strategy. PDGFs are required for normal kidney development by the recruitment of mesenchymal cells to both glomeruli and the interstitium. PDGFs are expressed in renal mesenchymal cells and, upon injury, in epithelial and infiltrating cells. They exert autocrine and paracrine effects on PDGF receptor-bearing mesenchymal cells, i.e. mesangial cells, fibroblasts and vascular smooth-muscle cells, which are crucially involved in progressive renal diseases. Proliferation but also migration and activation of these mesenchymal cells are the major effects mediated by PDGFs. These actions predefine the major roles of PDGFs in renal pathology, particularly in mesangioproliferative glomerulonephritis and interstitial fibrosis. Whereas for the former, the role of PDGFs is very well described and established, the latter is increasingly better documented as well. An involvement of PDGFs in other renal diseases, e.g. acute kidney injury, vascular injury and hypertensive as well as diabetic nephropathy, is less well established or presently unknown. Nevertheless, PDGFs represent a promising therapeutic option for progressive renal diseases, especially those characterized by mesangial cell proliferation and interstitial fibrosis. Clinical studies are eagerly awaited, in particular, since several drugs inhibiting PDGF signalling are available for clinical testing.