An Update on the Role of Growth Factors in the Development of Diabetic Kidney Disease

Abstract

Various growth factors have been proposed to be players in different areas of diabetes mellitus including a possible relationship to the characteristic changes in metabolism and development of complications. In particular, growth hormone (GH) and insulin-like growth factors (IGFs) system have a long and distinguished history with relation both to the diabetic metabolic aberration and the pathogenesis of diabetic angiopathy. The published evidence covering this area has recently been reviewed [1–3]. Further, substantial evidence has suggested that some growth factors (i.e. GH and IGFs, epidermal growth factor (EGF), transforming growth factor β (TGF-β), platelet derived growth factor (PDGF), tumor necrosis factor a (TNF-α) and fibroblastic growth factors (FGFs)) have conceivable effects on the development of renal complications in diabetes as reviewed in The Kidney and Hypertension in Diabetes Mellitus, 2th Edition, 1994 [4]. The present review is an update of the topic with emphasis on three of the above mentioned growth factor systems and a new promising candidate, i.e. vascular endothelial growth factor (VEGF). The first part of the review presents an update for a definite role of the GH/IGF system in the pathogenesis of the renal changes in experimental diabetes with focus on the renoprotective effects of long-acting somatostatin analogues and GH-receptor antagonists. In the second and third part, an update of the literature suggesting a causal role for EGF and TGF-β in the patogenesis of diabetic renal changes is presented and in the fourth part the new evidence of VEGF being involved in the development of diabetic kidney disease is given.