The role of Tenascin X in gut function

The project’s aim is to understand how abnormalities of Tenascin X (TNX) lead to gastrointestinal dysfunction and symptoms.

Specifically, i) to determine where in the normal gut TNX is found – which cells and tissues express TNX (neuronal, muscular, epithelial or otherwise); ii) to identify the functional role of TNX-expressing cells; iii) to determine the role of TNX in functional responses of the gut to electrical and natural stimulation and iv) to determine the gut phenotype (symptoms and function) of patients with EDS-HT.

Researchers

The Principal Investigator is Professor Qasim Aziz, Director of the Wingate Institute of Neurogastroenteroloy and the Secondary Supervisor is Professor Ashley Blackshaw, Professor of Enteric Neuroscience at Queen Mary University of London. The project is a PhD study for Ruby Aktar.

Why study the role of Tenascin X in gut function?

This project leads on from the previously funded project examining connective tissue and functional gastrointestinal disorders. Bowel & Cancer Research is funding this work because individuals often suffer a markedly poor quality of life with a range of symptoms from bloating, reflux, diahorrea, chronic pain and severe food intolerances.

As the condition is so poorly understood, these individuals are often subjected to unfair labelling, such as being a hypochondriac, a fussy eater or someone with an eating disorder.

The team at the Wingate Institute under the direction of Professor Aziz are leading research efforts in this area and are well placed to make progress.

Progress

The project successfully secured funding from Bowel & Cancer Research in its November 2013 funding round to continue the programme of work that was undertaken during the proof-of-principal funding. In 2015 the Henry Smith Charity agreed to support the work, funding further investigation into the role of TNX and bowel dysfunction in Ehlers Danlos Syndrome.

In 2016 Ruby successfully passed her PhD and is detailing novel findings from the project in a manscript for the scientific journal GUT. Her main and novel findings were that Tenascin X is found around gut neuronal structures (relating to neurons) and a loss of the Tenascin X gene results in disordered function of the stomach as well as the colon. Patients without Tenascin X, experience symptoms such as increased reflux, abdominal pain and bloating.

Therefore the research has concluded that Tenascin X is important in gut function and could provide a useful target for the development of future therapies. This is particularly significant for people with joint hypermobility where TNX is related to this hypermobility. For now, patients with TNX deficiency can be better identified and their treatment better managed.

An MRC/Wellcome post doctoral fellowship application is now being prepared to enable Dr Aktar to continue these studies, and we wish the team well with this.