Upregulation of matrix metalloproteinase-9 dependent on hyaluronan synthesis after sciatic nerve injury.

Using a rat chronic constriction injury (CCI) model, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) after sciatic nerve injury and its relationship with hyaluronan (HA). MMP-9 expression and activity were induced after the nerve injury. We found that CCI rats with oral administration of 4-methylunbelliferone (4-MU), which was a hyaluronan synthases inhibitor, exhibited reduced MMP-9 activity and mRNA expression compared with CCI rats that were not given 4-MU. MMP modulatory factors, such as TIMPs and uPA, did not change after the 4-MU was administered. This result indicated that the upregulation of MMP-9 after nerve injury in CCI rats was dependent on HA synthesis and was useful for the treatment of nerve injuries.