Wound healing-related properties detected in an experimental model with a collagen gel contraction assay are affected in the absence of tenascin-X
Wound healing-related properties detected in an experimental model with a collagen gel contraction assay are affected in the absence of tenascin-X
复制标题
DOI：
10.1016/j.yexcr.2017.12.025
复制
发表时间：
2018-02-15
影响因子：
3.7
通讯作者：
Matsumoto, Ken-ichi
中科院分区：
文献类型：
--
作者：
Hashimoto, Kei;Kajitani, Naoyo;Matsumoto, Ken-ichi
与典型性EDS患者不同，Tenascin-X(TNX)缺陷型Ehler-Danlos综合征(EDS)患者不会表现出伤口愈合延迟，后者表现出胶原基因突变。同样，在TnX基因敲除(KO)小鼠中，皮肤伤口闭合是正常的，即使这些小鼠表现出断裂强度降低。因此，我们推测在没有TnX的情况下，伤口的愈合过程可能会受到影响。在这项研究中，为了研究缺乏TNX对伤口愈合相关特性的影响，我们用野生型(WT)和TNX-KO小鼠胚胎成纤维细胞(MEF)进行了胶原凝胶收缩试验。含有TNX-KO MEF的胶原凝胶的收缩明显大于含有WT MEF的胶原凝胶。随后，我们检测了胶原凝胶的收缩相关特性，如基质金属蛋白酶-2和基质金属蛋白酶-9的活性以及胶原凝胶中转化生长因子131的蛋白和mRNA的表达水平。在不加TNX的情况下，基质金属蛋白酶-2和基质金属蛋白酶-9的活性及转化生长因子-β1的表达水平均升高。此外，在没有TNX的情况下，MEF丝状突起的形成、细胞的增殖、迁移和胶原的表达都得到了促进。这些结果表明，在缺乏TNX的细胞外环境中，这些与伤口愈合相关的特性会受到影响。
Patients with tenascin-X (TNX)-deficient type Ehlers-Danlos syndrome (EDS) do not exhibit delayed wound healing, unlike classic type EDS patients, who exhibit mutations in collagen genes. Similarly, in TNX-knockout (KO) mice, wound closure of the skin is normal even though these mice exhibit a reduced breaking strength. Therefore, we speculated that the wound healing process may be affected in the absence of TNX. In this study, to investigate the effects of TNX absence on wound healing-related properties, we performed collagen gel contraction assays with wild-type (WT) and TNX-KO mouse embryonic fibroblasts (MEFs). Collagen gels with embedded TNX-KO MEFs showed significantly greater contraction than those containing WT MEFs. Subsequently, we assessed collagen gel contraction-related properties, such as the activities of matrix metalloproteinase (MMP)-2 and MMP-9 and the protein and mRNA expression levels of transforming growth factor 131 (TGF-beta 1) in the collagen gels. The activities of MMP-2 and MMP-9 and the expression level of TGF-beta 1 were elevated in the absence of TNX. Furthermore, filopodia-like protrusion formation, cell proliferation, migration, and collagen expression in MEFs were promoted in the absence of TNX. These results indicate that these wound healing-related properties are affected in a TNX-deficient extracellular environment.