Expression and effects of matrix metalloproteinase 2 and 9 and tissue inhibitor of metalloproteinase 1 and 2 in the denervated skeletal muscle of rats / 中国组织工程研究

ABSTRACT

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP) are involved in the remodeling of extracellular matrix under normal or pathological conditions, and the positive expression of MMP-2 and MMP-9 has been shown to play important physiological and pathological roles in the denervated skeletal muscle. OBJECTIVE: To investigate the expression and effect of MMP-2 and MMP-9 and their tissue inhibitors (TIMP-1 and TIMP-2) in the denervated skeletal muscle. METHODS: The right sciatic nerve of rats was cut off to establish the model of denervated skeletal muscle, and the right skeletal muscle of rats was harvested after different intervals. The morphologic changes of the denervated skeletal muscle were detected through hematoxylin-eosin staining, immunohistochemical staining, and RT-PCR. The expression and change of MMP-2 and MMP-9 and TIMP-1 and TIMP-2 were compared with the sham operation group. RESULTS AND CONCLUSION: Atrophy and fibrosis were observed in the denervated skeletal muscle. There was a rapid increase of MMP-2 and TIMP-2 with double peaks at the 3rdand 56thdays after modeling; at the 3rdand 70thdays, the expression of MMP-9 increased significantly and reached the peak respectively; mRNA level of TIMP-1 only increased in the early stage, reached the peak at the 3rdday and gradual declined to normal level, without the second peak. To conclude, MMPs and TIMPs are involved in the tissue changes following denervation. TIMP-1 and TIMP-2 have a protective role in the remodeling progression. The altered balance between MMPs and TIMPs in the late stage of denervation may be responsible for extracellular matrix degradation leading to the atrophy and fibrosis progression.