Extracellular matrix of peripheral nerves in diabetes

Peripheral nerves are susceptible to develop multiple changes in their morphology and biochemical composition as consequences of diabetes mellitus. This review focuses on diabetes-induced alterations of the extracellular matrix of the peripheral nerves, and on the potential molecular mechanisms causing these changes. The interest towards the extracellular matrix of peripheral nerves of diabetic patients is highlighted by the fact that the extracellular matrix does not only mechanically support the cells which it surrounds, but it also regulates their behavior through specific interactions mediated via molecules on the cell surface, such as integrin receptors and cell surface proteoglycans. Thus, changes in the structure and composition of the extracellular matrix may alter cellular functions in multiple ways. At the ultrastructural level, these changes include e.g. thickening of vascular, perineurial and Schwann cell associated basement membranes; accumulation of microfibrillar material in the vicinity of perineurial cells; and increased diameter of endoneurial collagen fibrils. At the molecular level, the changes may be associated with altered metabolism of various collagen types, such as type I, III, IV and VI collagens.