UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

A novel role for the extracellular matrix glycoprotein-Tenascin-X in gastric function

Aktar, R; Peiris, M; Fikree, A; Eaton, S; Kritas, S; Kentish, SJ; Araujo, EJA; ... Blackshaw, LA; + view all (2019) A novel role for the extracellular matrix glycoprotein-Tenascin-X in gastric function. Journal of Physiology 10.1113/JP277195. (In press).

[img] Text
Aktar_JP_accepted.pdf - ["content_typename_Accepted version" not defined]
Access restricted to UCL open access staff until 4 July 2019.

Download (1MB)

Abstract

Tenascin X (TNX) is a glycoprotein that regulates tissue structure through anti‐adhesive interactions with collagen in the extracellular matrix. TNX deficiency causes a phenotype similar to hypermobility Ehlers Danlos Syndrome (hEDS) involving joint hypermobility, skin hyperelasticity, pain and gastrointestinal (GI) dysfunction. Previously, we have shown 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 set out to identify if 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 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 GABAB receptor agonist. There were no changes in nodose ganglia excitability in TNX deficient mice suggesting vagal afferent responses are likely due to altered peripheral mechanosensitivity. In TNXB‐deficient patients significantly greater symptoms of reflux, indigestion, and abdominal pain was reported. Here we report the first role for TNX in gastric function and further studies are required in TNX deficient patients to determine if symptoms can be relieved using GABAB agonists.

Type: Article
Title: A novel role for the extracellular matrix glycoprotein-Tenascin-X in gastric function
DOI: 10.1113/JP277195
Publisher version: https://doi.org/10.1113/JP277195
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: enteric neurones, gastric emptying, gastric hypersensitivity
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Development Bio and Cancer Prog
URI: http://discovery.ucl.ac.uk/id/eprint/10065542
Downloads since deposit
1Download
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item