Okuda-Ashitaka Emiko, Matsumoto Ken-Ichi
Department of Biomedical Engineering, Osaka Institute of Technology, Osaka, Japan.
Department of Biosignaling and Radioisotope Experiment, Interdisciplinary Center for Science Research, Head Office for Research and Academic Information, Shimane University, Izumo, Japan.
Front Genet. 2023 Mar 15;14:1107787. doi: 10.3389/fgene.2023.1107787. eCollection 2023.
Tenascin-X (TNX) is an extracellular matrix glycoprotein for which a deficiency results in a recessive form of classical-like Ehlers-Danlos syndrome (clEDS), a heritable connective tissue disorder with hyperextensible skin without atrophic scarring, joint hypermobility, and easy bruising. Notably, patients with clEDS also suffer from not only chronic joint pain and chronic myalgia but also neurological abnormalities such as peripheral paresthesia and axonal polyneuropathy with high frequency. By using TNX-deficient ( ) mice, well-known as a model animal of clEDS, we recently showed that mice exhibit hypersensitivity to chemical stimuli and the development of mechanical allodynia due to the hypersensitization of myelinated A-fibers and activation of the spinal dorsal horn. Pain also occurs in other types of EDS. First, we review the underlying molecular mechanisms of pain in EDS, especially that in clEDS. In addition, the roles of TNX as a tumor suppressor protein in cancer progression have been reported. Recent large-scale database analyses have shown that TNX is downregulated in various tumor tissues and that high expression of TNX in tumor cells has a good prognosis. We describe what is so far known about TNX as a tumor suppressor protein. Furthermore, some patients with clEDS show delayed wound healing. mice also exhibit impairment of epithelial wound healing in corneas. TNX is also involved in liver fibrosis. We address the molecular mechanism for the induction of by the expression of both a peptide derived from the fibrinogen-related domain of TNX and integrin α11.
腱生蛋白-X（TNX）是一种细胞外基质糖蛋白，其缺乏会导致隐性形式的经典型埃勒斯-当洛综合征（clEDS），这是一种遗传性结缔组织疾病，表现为皮肤过度伸展且无萎缩性瘢痕、关节活动过度和易瘀伤。值得注意的是，clEDS患者不仅患有慢性关节疼痛和慢性肌痛，还经常出现外周感觉异常和轴索性多发性神经病等神经异常症状。通过使用作为clEDS模型动物而闻名的TNX缺陷小鼠，我们最近发现，该小鼠对化学刺激表现出超敏反应，并由于有髓鞘A纤维的超敏化和脊髓背角的激活而出现机械性异常性疼痛。疼痛也发生在其他类型的EDS中。首先，我们回顾EDS中疼痛的潜在分子机制，特别是clEDS中的机制。此外，已有报道称TNX作为一种肿瘤抑制蛋白在癌症进展中的作用。最近的大规模数据库分析表明，TNX在各种肿瘤组织中表达下调，并且肿瘤细胞中TNX的高表达具有良好的预后。我们描述了目前已知的TNX作为肿瘤抑制蛋白的情况。此外，一些clEDS患者表现出伤口愈合延迟。TNX缺陷小鼠的角膜上皮伤口愈合也受损。TNX还参与肝纤维化。我们探讨了由TNX纤维蛋白原相关结构域衍生的肽和整合素α11的表达诱导肝纤维化的分子机制。
