MMP-3 provokes CTGF/CCN2 production independently of protease activity and dependently on dynamin-related endocytosis, which contributes to human dental pulp cell migration
MMP-3 provokes CTGF/CCN2 production independently of protease activity and dependently on dynamin-related endocytosis, which contributes to human dental pulp cell migration
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DOI：
10.1002/jcb.24007
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发表时间：
2012-04-01
影响因子：
4
通讯作者：
Matsushima, Kiyoshi
中科院分区：
文献类型：
--
作者：
Muromachi, Koichiro;Kamio, Naoto;Matsushima, Kiyoshi
基质金属蛋白酶-3（MMP-3）的表达在活髓切断术后被促进，并且在活髓切断术后将MMP-3应用于牙髓促进血管生成和硬组织形成。然而，MMP-3促进牙髓创伤愈合的机制仍不清楚。结缔组织生长因子/CCN家族2（CTGF/CCN 2）是一种属于CCN家族的蛋白质，被认为参与伤口愈合、血管生成和细胞迁移。在这项研究中，我们研究了CTGF/CCN 2参与MMP-3诱导的人牙髓（成纤维细胞样）细胞的细胞迁移。在人牙髓细胞中，MMP-3促进细胞迁移，但这种作用在抗CTGF/CCN 2抗体的存在下被明显阻断。MMP-3以浓度和时间依赖性方式刺激CTGF/CCN 2的mRNA和蛋白表达和分泌。MMP-3抑制剂NNGH不能抑制MMP-3诱导的CTGF/CCN 2蛋白表达。有效的发动蛋白抑制剂dynasore明显抑制MMP-3诱导的CTGF/CCN 2表达。这些结果强烈表明，MMP-3诱导CTGF/CCN 2的生产独立的MMP-3的蛋白酶活性和依赖于动力蛋白相关的内吞作用，这是参与在人牙髓细胞的细胞迁移。J.细胞。113：13481358，2012。(c)2011年威利期刊公司
Matrix metalloproteinase-3 (MMP-3) expression is promoted after pulpotomy, and application of MMP-3 to dental pulp after pulpotomy accelerates angiogenesis and hard tissue formation. However, the mechanism by which MMP-3 promotes dental pulp wound healing is still unclear. Connective tissue growth factor/CCN family 2 (CTGF/CCN2), a protein belonging to the CCN family, is considered to participate in wound healing, angiogenesis, and cell migration. In this study, we examined the involvement of CTGF/CCN2 in MMP-3-induced cell migration in human dental pulp (fibroblast-like) cells. In human dental pulp cells, MMP-3 promoted cell migration, but this effect was clearly blocked in the presence of anti-CTGF/CCN2 antibody. MMP-3 provoked mRNA and protein expression and secretion of CTGF/CCN2 in a concentration- and time-dependent manner. The MMP-3 inhibitor NNGH failed to suppress MMP-3-induced CTGF/CCN2 protein expression. The potent dynamin inhibitor dynasore clearly inhibited MMP-3-induced CTGF/CCN2 expression. These results strongly suggest that MMP-3 induces CTGF/CCN2 production independently of the protease activity of MMP-3 and dependently on dynamin-related endocytosis, which is involved in cell migration in human dental pulp cells. J. Cell. Biochem. 113: 13481358, 2012. (c) 2011 Wiley Periodicals, Inc.