Modulation of extracellular matrix components by metalloproteinases and their tissue inhibitors during degeneration and regeneration of rat sural nerve

Abstract

The success of peripheral nervous system regeneration has been associated with changes on the microenvironment, particularly on the extracellular matrix (ECM) components. In the present study we analyzed by indirect immunohistochemistry, electron microscopy and Western blotting, the distribution of ECM components, metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), during Wallerian degeneration (WD) and nerve regeneration (2nd, 7th and 21st days after injury) on crushed rat sural nerves. Our results showed that laminin α 3-chain and α 2-chain are over expressed during the early stages of degeneration and regeneration respectively, whereas type IV collagen expression increased progressively after crush. On the other hand, the expression of chondroitin sulfate was down regulated during the early stages of degeneration, returning progressively to normal values during nerve regeneration. The expression of MMP-3 was almost normal immediately after lesion, and then reduced progressively achieving the smallest expression at 21 days after crush; on the contrary, the expression of MMP-7 increased significantly immediately after crush (2nd day) returning to normal values afterwards. TIMP-1 and TIMP-2 were over expressed at the beginning of WD, returning progressively to normal values after that. These results indicate that the modifications of ECM components, which are favorable for nerve regeneration, are correlated with changes on the balance between MMPs and TIMPs.