A novel role for the extracellular matrix glycoprotein-Tenascin-X in gastric function
A novel role for the extracellular matrix glycoprotein-Tenascin-X in gastric function
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DOI：
10.1113/jp277195
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发表时间：
2019-03-15
影响因子：
5.5
通讯作者：
Blackshaw, L. Ashley
中科院分区：
文献类型：
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作者：
Aktar, Rubina;Peiris, Madusha;Blackshaw, L. Ashley
Tenascin-X （TNX）是一种糖蛋白，通过与细胞外基质中的胶原蛋白的抗粘附相互作用来调节组织结构。TNX缺乏导致的表型类似于活动过度的Ehlers-Danlos综合征，包括关节活动过度、皮肤过度弹性、疼痛和胃肠道功能障碍。之前，我们已经证明TNX是肠道神经控制所必需的，主要是胆碱能肠神经元的特定亚型，并调节小鼠结肠中伤害性感觉末梢的发芽和敏感性。这些发现与tnx缺乏患者和小鼠的症状相关。我们的目的是确定TNX是否相似地存在于小鼠和人类胃组织的神经结构中。然后，我们确定TNX是否具有功能性作用，特别是在胃运动和感觉功能以及结节神经节神经元中。我们报道TNX存在于小鼠和人胃的calretinin免疫反应性外源性神经末梢。TNX缺乏小鼠胃排空加速，迷走神经传入对胃膨胀的反应明显增加，可以用GABA(B)受体激动剂拯救。TNX缺陷小鼠的结节神经节兴奋性没有变化，这表明迷走神经传入反应可能是外周机械敏感性改变的结果。在tnxb缺乏的患者中，报告了明显更大的反流、消化不良和腹痛症状。在本研究中，我们报道了TNX在胃功能中的第一个作用。需要对TNX缺乏患者进行进一步研究，以确定使用GABA(B)激动剂是否可以缓解症状。
Tenascin-X (TNX) is a glycoprotein that regulates tissue structure via anti-adhesive interactions with collagen in the extracellular matrix. TNX deficiency causes a phenotype similar to hypermobility Ehlers-Danlos syndrome involving joint hypermobility, skin hyperelasticity, pain and gastrointestinal dysfunction. Previously, we have shown that TNX is required for neural control of the bowel by a specific subtype of mainly cholinergic enteric neurones and regulates sprouting and sensitivity of nociceptive sensory endings in mouse colon. These findings correlate with symptoms shown by TNX-deficient patients and mice. We aimed to identify whether TNX is similarly present in neural structures found in mouse and human gastric tissue. We then determined whether TNX has a functional role, specifically in gastric motor and sensory function and nodose ganglia neurones. We report that TNX was present in calretinin-immunoreactive extrinsic nerve endings in mouse and human stomach. TNX deficient mice had accelerated gastric emptying and markedly increased vagal afferent responses to gastric distension that could be rescued with GABA(B) receptor agonist. There were no changes in nodose ganglia excitability in TNX deficient mice, suggesting that vagal afferent responses are probably the result of altered peripheral mechanosensitivity. In TNXB-deficient patients, significantly greater symptoms of reflux, indigestion and abdominal pain were reported. In the present study, we report the first role for TNX in gastric function. Further studies are required in TNX deficient patients to determine whether symptoms can be relieved using GABA(B) agonists.