Altered Esophageal Smooth Muscle Phenotype in Achalasia.

IF 3.3 3区 医学 Q2 CLINICAL NEUROLOGY
Journal of Neurogastroenterology and Motility Pub Date : 2024-04-30 Epub Date: 2023-08-02 DOI:10.5056/jnm23024
David M Rodrigues, Sandra R Lourenssen, Jay Kataria, William G Paterson, Michael G Blennerhassett, Robert Bechara
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引用次数: 0

Abstract

Background/aims: Achalasia is a disorder characterized by impairment in lower esophageal sphincter relaxation and esophageal aperistalsis, caused primarily by loss of inhibitory innervation. However, little is known about associated changes in esophageal smooth muscle. We examined the contractile phenotype and innervation of the circular smooth muscle, as well as inflammatory status, and correlated these with patient-specific parameters.

Methods: Circular smooth muscle biopsies were obtained in consecutive patients with achalasia undergoing peroral endoscopic myotomy. Axonal innervation and neurotransmitter subtypes were determined with immunocytochemistry, and this was used with quantitative Polymerase Chain Reaction (qPCR) to characterize smooth muscle proliferation and cellular phenotype, as well as collagen expression. These were compared to control tissue obtained at esophagectomy and correlated with patient demographic factors including age, onset of symptoms, and Eckhardt score.

Results: Biopsies of smooth muscle were obtained from 25 patients with achalasia. Overall, there was increased mast cell number and collagen deposition but increased smooth muscle cell proliferation vs control. There was a striking drop in axon density over controls, with no differences among subtypes of achalasia. Immunocytochemical analysis showed increased expression of the contractile marker α-smooth muscle actin, principally in Type 1 achalasia, that increased with disease duration, while qPCR identified increased mRNA for smoothelin with decreased myosin heavy chain and collagen 3a1, but not collagen 1a1.

Conclusions: The thickened circular smooth muscle layer in achalasia is largely denervated, with an altered contractile phenotype and fibrosis. Biopsies obtained during peroral endoscopic myotomy provide a means to further study the pathophysiology of achalasia.

食管炎的食管平滑肌表型改变
背景/目的:食道下段括约肌松弛症是一种以食道下段括约肌松弛和食道蠕动障碍为特征的疾病,其主要原因是食道下段括约肌失去了抑制性神经支配。然而,人们对食管平滑肌的相关变化知之甚少。我们研究了环形平滑肌的收缩表型和神经支配以及炎症状态,并将其与患者的特定参数联系起来:方法:对连续接受口周内镜下肌切开术的贲门失弛缓症患者进行环状平滑肌活检。用免疫细胞化学法确定轴突支配和神经递质亚型,并将其与定量聚合酶链式反应(qPCR)相结合,确定平滑肌增殖和细胞表型以及胶原表达的特征。这些结果与食管切除术中获得的对照组织进行了比较,并与患者的人口统计学因素(包括年龄、发病症状和埃卡评分)相关联:结果:25 名贲门失弛缓症患者的平滑肌活检组织中发现了肥大细胞。总体而言,与对照组相比,肥大细胞数量和胶原沉积增加,但平滑肌细胞增殖增加。与对照组相比,轴突密度明显下降,但不同亚型弛缓症之间没有差异。免疫细胞化学分析显示,收缩标志物α-平滑肌肌动蛋白的表达增加,主要是在1型贲门失弛缓症中,且随病程延长而增加,而qPCR发现平滑肌蛋白的mRNA增加,肌球蛋白重链和胶原3a1减少,但胶原1a1没有减少:贲门失弛缓症患者增厚的环状平滑肌层在很大程度上被去神经化,收缩表型发生改变并出现纤维化。口周内窥镜肌切开术中获得的活组织样本为进一步研究贲门失弛缓症的病理生理学提供了一种方法。
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来源期刊
Journal of Neurogastroenterology and Motility
Journal of Neurogastroenterology and Motility GASTROENTEROLOGY & HEPATOLOGY-CLINICAL NEUROLOGY
CiteScore
6.30
自引率
8.80%
发文量
96
期刊介绍: Journal of Neurogastroenterology and Motility (J Neurogastroenterol Motil) is a joint official journal of the Korean Society of Neurogastroenterology and Motility, the Thai Neurogastroenterology and Motility Society, the Japanese Society of Neurogastroenterology and Motility, the Indian Motility and Functional Disease Association, the Chinese Society of Gastrointestinal Motility, the South East Asia Gastro-Neuro Motility Association, the Taiwan Neurogastroenterology and Motility Society and the Asian Neurogastroenterology and Motility Association, launched in January 2010 after the title change from the Korean Journal of Neurogastroenterology and Motility, published from 1994 to 2009.
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