The findings also link a TNX deficiency to increased abdominal pain, constipation, and diarrhea in hEDS patients.
The research, “The extracellular matrix glycoprotein tenascin-X regulates peripheral sensory and motor neurons,” was published in The Journal of Physiology.
Tenascin X, a component of a group of glycoproteins — proteins with a sugar chemical group attached — is found in the skin and joints’ extracellular matrix (ECM), which provides cells with biochemical and structural support. TNX interacts with collagen.
Different EDS subtypes have been linked to collagen or tenascin disorders. A deficiency in tenascin X has also been associated with skin tissue fragility and musculoskeletal pain, manifestations seen in hEDS, the most common type of Ehlers-Danlos.
Gastrointestinal symptoms — including abdominal pain, constipation, and lower gut motility — are common in hEDS patients, particularly in cases of TNX deficiency, and correlate with disease severity.
Patients with hEDS also show an increased incidence of irritable bowel syndrome, indicating a link between these two disorders. Of note, a subset of patients with bowel symptoms also have tenascin X deficiency.
Given this common occurrence of gastrointestinal manifestations in hypermobile EDS and tenascin X-deficient patients, a team from the U.K. and the Netherlands hypothesized that TNX is required for sensorimotor function of the colon. They also hypothesized that understanding the link between hEDS and bowel symptoms may help in the design or optimization of treatments.
The scientists conducted a detailed assessment of colon function, including the study of its gross anatomy, motor coordination, and nerve activity.
They found that, in both mice and humans (cancer patients undergoing colon removal), TNX was mainly found in the cell body of cholinergic enteric neurons — acetylcholine-producing nerve cells that control gut movement, fluid exchange, and local blood flow in the colon.
“Thus, TNX may play a different role in the gut compared with other tissues,” the researchers wrote.
Researchers also observed that mice lacking TNX had internal rectal prolapse (a condition in which the rectum slides through the anal opening) and loss of colon motility. These TNX-deficient mice also showed more pain-sensing nerves with greater sensitivity.
The study also assessed data from questionnaires made to 11 hEDS patients (eight women) with TNX deficiency on five different domains — reflux, abdominal pain, constipation, indigestion, and diarrhea.
Data from these patients were compared to a reference Swedish population with 2,162 individuals.
Results showed that tenascin X-deficient individuals had increased abdominal pain (65%), constipation (32%), and diarrhea (64%) compared to controls. Three patients reported external rectal prolapse.
According to an Ehlers-Danlos Society release written by Rubina Aktar, PhD, the study’s first author, the study revealed that hEDS patients “have similar symptoms to those found in our mouse model.”
“Our novel paper, the first of its kind, suggests that TNX has unique functions in gut tissues — firstly, a role in gut nerves that affect bowel movements, and secondly, a role in influencing pain-sensing nerves,” Aktar wrote.
The research team suggests that “TNX genotype should be evaluated routinely in hEDS patients to better understand its role in specific symptoms, and thus allow targeted treatment.”
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