MATRIX METALLOPROTEINASES MMP-2 AND MMP-9 IN DENERVATED MUSCLE AND INJURED NERVE

Nerve crush or axotomy results in a transient or longterm denervation accompanied by remodelling in nerve, muscle and neuromuscular junction s, These changes include an increased turnover of several extracellula r matrix molecules and proliferation of Schwann cells in injured nerve s, Given the role of matrix degrading metalloproteinases MMP-2 and MMP -9 (gelatinases-type IV collagenases) in extracellular matrix remodell ing, we investigated their regulation and activation in denervated mus cles and injured nerves in mice. For this, immunofluorescence using MM P-2 and MMP-9 antibodies was carried concomitantly with gelatin zymogr aphy and quantification of gelatinase activity using [H-3]- gelatin su bstrate. Results show that in normal mouse muscles MMP-2 and MMP-9 are localized at the neuromuscular junctions, in Schwann cells and the pe rineurium of the intramuscular nerves. In denervated mouse muscles, MM P-2 immunolabelling persists at the neuromuscular junctions but decrea ses in the nerves whereas MMP-9 immunolabelling persists at the neurom uscular junctions but is enhanced in degenerated intramuscular nerves. Denervated muscles did not show any significant change of gelatinolyt ic activity or expression pattern, while injured nerves exhibited a tr ansient increase of MMP-9 and activation of MMP-2. In conclusion, this study demonstrates that MMP-2 and MMP-9 are expressed at mouse neurom uscular junctions and that their localization and expression pattern a ppear not to be modified by denervation. Their modulation in injured n erves suggests they are involved in axonal degeneration and regenerati on.