Role of growth factors in the development of diabetic complications

Abstract

The structural changes characterising diabetic microangiopathy, which may be referred to as 'abnormal growth' and 'impaired regeneration', strongly suggest a role for a number of aberrantly expressed growth factors, possibly acting in combination, in the development of these complications. This initial speculation has been supported by the detection of increased concentrations of several growth factors in the target tissues of diabetic long-term complications, and by enhanced expression of these growth factors consequent to the activation of the biochemical pathways linking hyperglycaemia to microvascular changes: the polyol pathway; non-enzymatic glycation of proteins; vasoactive hormones; oxidative stress, and hyperglycaemic pseudohypoxia. As to nephropathy, insulin-like growth factor I (IGF-I) seems to be implicated in the earlier stages of the disease, while transforming growth factor beta (TGF beta) is involved both in the early and later stages, being responsible, at least in part, for extracellular matrix (ECM) accumulation. Vascular endothelial growth factor (VEGF) plays a pivotal role both in non-proliferative and proliferative retinopathy. Finally, deficiency of several neurotrophic factors, namely nerve growth factor (NGF) and IGF-I has been related to the degeneration or impaired regeneration occurring in diabetic neuropathy. Knowledge of the involvement of growth factors in diabetic microangiopathy opens the way to new therapeutic interventions aimed at blocking the deleterious actions of several growth factors.