Extracellular matrix remodelling in human diabetic neuropathy

Abstract

The extracellular matrix of peripheral nerve plays a vital role in terms of normal nerve fibre function and also in the regenerative response following nerve injury. Nerve fibre loss is a major feature of diabetic neuropathy; however, the regenerative response is limited and this may be associated with changes in the composition of the extracellular matrix. Glycoproteins and collagens are major components of the extracellular matrix and are known to be important in terms of axonal growth. This work has therefore examined whether changes in the expression of two major glycoproteins, laminin and tenascin, and three collagen types (IV, V and VI) occur in the endoneurial and perineurial connective tissue compartments of human diabetic nerve. Despite being known to have a positive effect in terms of axonal growth, laminin levels were not elevated in the diabetic nerves. However, the pattern of tenascin expression did differ between the two groups being found in association with axon myelin units in the diabetic samples only. The pattern of collagen IV expression was the same in both tissue groups and was not found to be up-regulated. However, levels of collagen V and VI were both significantly increased in the endoneurium and for collagen VI also in the perineurium.

Fig. 1

A light micrograph of part of a fascicle from the negative control of a diabetic nerve sample. Staining is absent in both the perineurium (P) and the endoneurium (E).

Fig. 2

Light micrographs of control (left-hand column) and diabetic (right-hand column) immunostained nerve samples. (a,b) Laminin in both the perineurium (P) and endoneurium (E). (c,d) Tenascin staining is present in the perineurium of both groups and is also found in association with axon–myelin units (arrow) in the diabetic group only. (e,f) Collagen IV, (g,h) collagen V and (i,j) collagen VI.