Colonic mucosal TRPA1 expression profiles in irritable bowel syndrome and its correlation to symptom severity: An exploratory study

IF 3.2 4区 医学 Q2 NEUROSCIENCES
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
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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.
肠易激综合征结肠黏膜TRPA1表达谱及其与症状严重程度的相关性:一项探索性研究
内脏过敏是肠易激综合征(IBS)的一个标志。一些动物研究表明,瞬时受体电位锚蛋白-1 (TRPA1)阳离子通道可能参与其中。本研究的主要目的是评估肠易激综合征患者结肠黏膜中TRPA1的位置特异性表达及其与症状严重程度的相关性。方法对30例IBS患者进行乙状结肠活检(Rome III;中位年龄39.0岁,80%为女性)和23名健康对照(中位年龄22.7岁,43.5%为女性)。对24例IBS患者进行了近端结肠活检。通过定量逆转录-聚合酶链反应检测TRPA1的表达水平,归一化为GAPDH,并使用−2ΔCt方法评估相对mRNA值。在IBS患者中,评估症状并与TRPA1表达相关。结果IBS患者乙状结肠中TRPA1的相对表达明显高于健康对照组(P <;0.001)。在IBS患者中,乙状结肠活检组织中TRPA1的表达明显高于近端结肠样本(p <;0.001)。在乙状结肠或近端结肠样本中TRPA1表达与症状严重程度(腹部不适、腹痛和腹胀)无显著相关性。结论这些发现提示TRPA1相关通路在未来作为IBS治疗靶点的潜在作用。由于目前的探索性研究未发现TRPA1表达与症状严重程度之间的相关性,因此需要进一步研究TRPA1在ibs患者中表达升高及其部位特异性表达的临床相关性。
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来源期刊
CiteScore
5.80
自引率
7.40%
发文量
83
审稿时长
66 days
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.
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