{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:01:08Z","timestamp":1790524868869,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T00:00:00Z","timestamp":1548201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000852","name":"Henry Smith Charity","doi-asserted-by":"publisher","award":["NSCG1Q9R"],"award-info":[{"award-number":["NSCG1Q9R"]}],"id":[{"id":"10.13039\/501100000852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Tenascin X (TNX) functions in the extracellular matrix of skin and joints where it maintains correct intercellular connections and tissue architecture<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>TNX is associated exclusively with vagal\u2010afferent endings and some myenteric neurones in mouse and human stomach, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>TNX\u2010deficient mice have accelerated gastric emptying and hypersensitivity of gastric vagal mechanoreceptors that can be normalized by an inhibitor of vagal\u2010afferent sensitivity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cultured nodose ganglion neurones showed no changes in response to capsaicin, cholecystokinin and potassium chloride in TNX\u2010deficient mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>TNX\u2010deficient patients have upper gastric dysfunction consistent with those in a mouse model. Our translational studies suggest that abnormal gastric sensory function may explain the upper gut symptoms present in TNX deficient patients, thus making it important to study gastric physiology.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>TNX deficiency should be evaluated routinely in patients with connective tissue abnormalities, which will enable a better understanding of its role and allow targeted treatment. For example, inhibitors of vagal afferents\u2010baclofen could be beneficial in patients. These hypotheses need confirmation via targeted clinical trials.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Tenascin\u2010X (TNX) is a glycoprotein that regulates tissue structure via anti\u2010adhesive interactions with collagen in the extracellular matrix. TNX deficiency causes a phenotype similar to hypermobility Ehlers\u2013Danlos 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\u2010deficient 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\u2010immunoreactive 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<jats:sub>B<\/jats:sub> 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\u2010deficient 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<jats:sub>B<\/jats:sub> agonists.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277195","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T16:52:58Z","timestamp":1546534378000},"page":"1503-1515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A novel role for the extracellular matrix glycoprotein\u2010Tenascin\u2010X in gastric function"],"prefix":"10.1113","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8268-1820","authenticated-orcid":false,"given":"Rubina","family":"Aktar","sequence":"first","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madusha","family":"Peiris","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Fikree","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Eaton","sequence":"additional","affiliation":[{"name":"Institute of Child Health University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stamatiki","family":"Kritas","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute University of Adelaide  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Kentish","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute University of Adelaide  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo J. A.","family":"Araujo","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"},{"name":"Department of Histology Centre for Biological Sciences State University of Londrina  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano","family":"Bacarin","sequence":"additional","affiliation":[{"name":"Department of Histology Centre for Biological Sciences State University of Londrina  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-5865","authenticated-orcid":false,"given":"Amanda J.","family":"Page","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute University of Adelaide  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol C.","family":"Voermans","sequence":"additional","affiliation":[{"name":"Department of Neurology Radboud University Medical Centre  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qasim","family":"Aziz","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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