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Role of growth factors in the development of diabetic complications
F Chiarelli1, F Santilli, A Mohn
1Department of Medicine, Division of Paediatrics, University of Chieti, Italy. chiarelli@unich.it
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.
Insights
Aberrantly expressed growth factors contribute to diabetic microangiopathy complications. Targeting these growth factors offers new therapeutic strategies for conditions like nephropathy, retinopathy, and neuropathy.
Area of Science:
- Endocrinology
- Molecular Biology
- Pathology
Background:
- Diabetic microangiopathy involves structural changes like abnormal growth and impaired regeneration.
- Aberrant expression of growth factors is strongly implicated in the development of diabetic complications.
- Biochemical pathways activated by hyperglycemia contribute to microvascular changes.
Purpose of the Study:
- To explore the role of growth factors in diabetic microangiopathy.
- To identify specific growth factors involved in diabetic nephropathy, retinopathy, and neuropathy.
- To highlight the therapeutic potential of targeting growth factors.
Main Methods:
- Detection of growth factor concentrations in affected tissues.
- Analysis of growth factor expression linked to hyperglycemia-induced pathways.
- Review of literature on growth factor involvement in diabetic complications.
Main Results:
- Increased concentrations of several growth factors found in diabetic complication target tissues.
- Insulin-like growth factor I (IGF-I) implicated in early nephropathy; Transforming growth factor beta (TGF beta) in early/late nephropathy and ECM accumulation.
- Vascular endothelial growth factor (VEGF) crucial in retinopathy; neurotrophic factors (NGF, IGF-I) linked to neuropathy.
Conclusions:
- Growth factors play a significant role in the pathogenesis of diabetic microangiopathy.
- Specific growth factors are associated with distinct diabetic complications.
- Understanding growth factor involvement paves the way for novel therapeutic interventions.