Sylvester R. Groen , Daniel Keszthelyi , Ellen Wilms , Justin Huig , Pan Xu , Montserrat Elizalde , Lisa Vork , Daisy M.A.E. Jonkers , Zsuzsanna Helyes , Ad A.M. Masclee , Zsa Zsa R.M. Weerts
{"title":"Colonic mucosal TRPA1 expression profiles in irritable bowel syndrome and its correlation to symptom severity: An exploratory study","authors":"Sylvester R. Groen , Daniel Keszthelyi , Ellen Wilms , Justin Huig , Pan Xu , Montserrat Elizalde , Lisa Vork , Daisy M.A.E. Jonkers , Zsuzsanna Helyes , Ad A.M. Masclee , Zsa Zsa R.M. Weerts","doi":"10.1016/j.autneu.2025.103273","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Visceral hypersensitivity is a hallmark of irritable bowel syndrome (IBS). A putative involvement of the Transient Receptor Potential Ankyrin-1 (TRPA1) cation channel has been suggested by several animal studies. Main objective of this study is to assess location-specific TRPA1 expression in the colonic mucosa and its correlation with symptom severity in IBS patients.</div></div><div><h3>Methods</h3><div>Biopsies were obtained from the sigmoid of 30 IBS patients (Rome III; median age 39.0 years, 80 % female) and 23 healthy controls (median age 22.7 years, 43.5 % female). Additional biopsies of the proximal colon were obtained in 24 IBS patients. TRPA1 expression levels were measured in duplicate by quantitative reverse-transcriptase–polymerase-chain-reaction, normalized to GAPDH, and assessed as relative mRNA values using the −2<sup>ΔCt</sup> method. In IBS patients, symptoms were assessed and correlated with TRPA1 expression.</div></div><div><h3>Results</h3><div>Relative TRPA1 expression in the sigmoid was significantly higher in IBS patients compared to healthy controls (<em>P</em> < 0.001). Within IBS patients TRPA1 expression of sigmoid biopsies was significantly higher compared to proximal colon samples (<em>p</em> < 0.001). No significant correlation was found between TRPA1 expression in sigmoid or proximal colon samples and the symptom severity (abdominal discomfort, abdominal pain and bloating).</div></div><div><h3>Conclusion</h3><div>These findings suggest a potential role for the TRPA1 related pathway as a target for IBS treatment in the future. Since there was no correlation found in the current exploratory study between TRPA1 expression and symptom severity, further research towards the clinical relevance of the increased TRPA1 expression in IBS-patients along with its location-specific expression is warranted.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"259 ","pages":"Article 103273"},"PeriodicalIF":3.2000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autonomic Neuroscience-Basic & Clinical","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1566070225000359","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction
Visceral hypersensitivity is a hallmark of irritable bowel syndrome (IBS). A putative involvement of the Transient Receptor Potential Ankyrin-1 (TRPA1) cation channel has been suggested by several animal studies. Main objective of this study is to assess location-specific TRPA1 expression in the colonic mucosa and its correlation with symptom severity in IBS patients.
Methods
Biopsies were obtained from the sigmoid of 30 IBS patients (Rome III; median age 39.0 years, 80 % female) and 23 healthy controls (median age 22.7 years, 43.5 % female). Additional biopsies of the proximal colon were obtained in 24 IBS patients. TRPA1 expression levels were measured in duplicate by quantitative reverse-transcriptase–polymerase-chain-reaction, normalized to GAPDH, and assessed as relative mRNA values using the −2ΔCt method. In IBS patients, symptoms were assessed and correlated with TRPA1 expression.
Results
Relative TRPA1 expression in the sigmoid was significantly higher in IBS patients compared to healthy controls (P < 0.001). Within IBS patients TRPA1 expression of sigmoid biopsies was significantly higher compared to proximal colon samples (p < 0.001). No significant correlation was found between TRPA1 expression in sigmoid or proximal colon samples and the symptom severity (abdominal discomfort, abdominal pain and bloating).
Conclusion
These findings suggest a potential role for the TRPA1 related pathway as a target for IBS treatment in the future. Since there was no correlation found in the current exploratory study between TRPA1 expression and symptom severity, further research towards the clinical relevance of the increased TRPA1 expression in IBS-patients along with its location-specific expression is warranted.
期刊介绍:
This is an international journal with broad coverage of all aspects of the autonomic nervous system in man and animals. The main areas of interest include the innervation of blood vessels and viscera, autonomic ganglia, efferent and afferent autonomic pathways, and autonomic nuclei and pathways in the central nervous system.
The Editors will consider papers that deal with any aspect of the autonomic nervous system, including structure, physiology, pharmacology, biochemistry, development, evolution, ageing, behavioural aspects, integrative role and influence on emotional and physical states of the body. Interdisciplinary studies will be encouraged. Studies dealing with human pathology will be also welcome.