The extracellular matrix glycoprotein tenascin-X regulates peripheral sensory and motor neurones.
Rubina AktarMadusha PeirisAsma FikreeVincent Cibert-GotonMaxim WalmsleyIain R ToughPaulo da Silva WatanabeEduardo J A AraujoSahar D MohammedJean-Marie DelalandeDavid C BulmerS Mark ScottHelen M CoxNicol C VoermansQasim AzizL Ashley BlackshawPublished in: The Journal of physiology (2018)
The extracellular matrix (ECM) is not only an integral structural molecule, but is also critical for a wide range of cellular functions. The glycoprotein tenascin-X (TNX) predominates in the ECM of tissues like skin and regulates tissue structure through anti-adhesive interactions with collagen. Monogenic TNX deficiency causes painful joint hypermobility and skin hyperelasticity, symptoms characteristic of hypermobility Ehlers Danlos syndrome (hEDS). hEDS patients also report consistently increased visceral pain and gastrointestinal (GI) dysfunction. We investigated whether there is a direct link between TNX deficiency and GI pain or motor dysfunction. We set out first to learn where TNX is expressed in human and mouse, then determine how GI function, specifically in the colon, is disordered in TNX-deficient mice and humans of either sex. In human and mouse tissue, TNX was predominantly associated with cholinergic colonic enteric neurones, which are involved in motor control. TNX was absent from extrinsic nociceptive peptidergic neurones. TNX-deficient mice had internal rectal prolapse and a loss of distal colonic contractility which could be rescued by prokinetic drug treatment. TNX-deficient patients reported increased sensory and motor GI symptoms including abdominal pain and constipation compared to controls. Despite absence of TNX from nociceptive colonic neurones, neuronal sprouting and hyper-responsiveness to colonic distension was observed in the TNX-deficient mice. We conclude that ECM molecules are not merely support structures but an integral part of the microenvironment particularly for specific populations of colonic motor neurones where TNX exerts functional influences.
Keyphrases
- extracellular matrix
- end stage renal disease
- ejection fraction
- neuropathic pain
- newly diagnosed
- ulcerative colitis
- endothelial cells
- stem cells
- chronic pain
- pain management
- prognostic factors
- minimally invasive
- type diabetes
- emergency department
- induced pluripotent stem cells
- spinal cord injury
- metabolic syndrome
- high resolution
- physical activity
- spinal cord
- insulin resistance
- mass spectrometry
- patient reported outcomes
- brain injury
- skeletal muscle
- subarachnoid hemorrhage
- smoking cessation
- urinary incontinence