Tenascin-X（TNX）是一种细胞外基质糖蛋白，缺乏会导致隐性的经典型埃勒斯-丹洛斯综合症（clEDS），一种遗传性结缔组织紊乱，具有可伸展的皮肤、无萎缩疤痕、关节过度活动和易淤血的特征。值得注意的是，clEDS患者不仅患有慢性关节疼痛和慢性肌肉痛，还会出现神经系统异常，如周围神经痛和轴突多发性神经病高发率。最近，我们使用Tnxb - / -小鼠，这是一个已知的clEDS模型动物，表明Tnxb - / -小鼠对化学刺激过敏，并因髓鞘A-纤维的过敏和脊髓后角的激活而发展机械痛觉过敏。其他类型的EDS也会出现疼痛症状。首先，我们回顾了EDS的疼痛机制，特别是clEDS的机制。此外，已经报道了TNX作为癌症进展的肿瘤抑制蛋白的作用。最近的大规模数据库分析表明，TNX在各种肿瘤组织中下调，并且肿瘤细胞中TNX的高表达预后良好。我们描述了目前所知道的TNX作为肿瘤抑制蛋白的情况。此外，一些clEDS患者有延迟愈合的创伤。Tnxb - / -小鼠的角膜上皮愈合也受到损伤。TNX还参与肝纤维化。我们描述了由TNX的纤维蛋白原相关结构域肽和整合素α11表达诱导的COL1A1的分子机制。Copyright © 2023 Okuda-Ashitaka and Matsumoto.

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 (Tnxb -/-) mice, well-known as a model animal of clEDS, we recently showed that Tnxb -/- 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 in silico 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. Tnxb -/- 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 COL1A1 by the expression of both a peptide derived from the fibrinogen-related domain of TNX and integrin α11.Copyright © 2023 Okuda-Ashitaka and Matsumoto.