Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis.
Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis.
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DOI：
10.1177/1744806917705564
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发表时间：
2017-01
期刊：
影响因子：
3.3
通讯作者：
Koppán M
中科院分区：
文献类型：
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作者：
Bohonyi N;Pohóczky K;Szalontai B;Perkecz A;Kovács K;Kajtár B;Orbán L;Varga T;Szegedi S;Bódis J;Helyes Z;Koppán M
瞬时受体电位香草素1（TRPV 1）和瞬时受体电位锚蛋白1（TRPA 1）主要由初级感觉神经元表达，作为主要的伤害感受整合剂。它们也以雌激素调节的方式存在于大鼠子宫内膜上。TRPV1在腹膜和卵巢子宫内膜异位症患者中上调，但没有关于TRPA1及其病理生理意义的信息。在这项研究中，接受腹腔镜手术的患者进行了调查：由于直肠乙状结肠深部浸润性子宫内膜异位症（n = 15），子宫肌瘤引起的中度痛经（n = 7）和输卵管不孕症无痛（n = 6）。采用定量聚合酶链反应和半定量免疫组织化学方法检测TRPA1和TRPV1 mRNA和蛋白的表达。结果与包括疼痛强度在内的临床特征相关。TRPA1和TRPV1受体在mRNA和蛋白水平上在健康人子宫内膜中表达。在间质和上皮层中发现稀疏、分散的胞质TRPA 1和TRPV 1免疫阳性。我们检测到TRPV1基因在深部浸润性子宫内膜异位症病变中表达上调，TRPV1基因在深部浸润性子宫内膜异位症患者的自身对照子宫内膜中表达也升高。组织学评分显示，与对照样本相比，深部浸润性子宫内膜异位症基质和上皮之间以及深部浸润性子宫内膜异位症上皮中的TRPA 1和TRPV 1存在显著差异。此外，我们还检测到深部浸润性子宫内膜异位症患者间质TRPV1免疫阳性率升高。基质TRPA1和TRPV1免疫反应性与痛经严重程度密切相关，以及TRPV1在异位上皮细胞和巨噬细胞上的表达与性交困难密切相关。上皮TRPA1和间质TRPV1免疫阳性也与排便困难的严重程度呈正相关。我们首次提供了健康人子宫内膜中存在非神经元TRPA1受体的证据，并证实了TRPV1通道的表达。它们在直肠乙状结肠深部浸润性子宫内膜异位症病变中的上调以及与疼痛强度的相关性提示了其在疾病病理生理机制中的潜在作用。
Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) expressed mainly by primary sensory neurons function as major nociceptive integrators. They are also present on the rat endometrium in an oestrogen-regulated manner. TRPV1 is upregulated in peritoneal and ovarian endometriosis patients, but there is no information about TRPA1 and their pathophysiological significances. In this study, patients undergoing laparoscopic surgery were investigated: severe dysmenorrhoea due to rectosigmoid deep infiltrating endometriosis (n = 15), uterine fibroid-induced moderate dysmenorrhoea (n = 7) and tubal infertility with no pain (n = 6). TRPA1 and TRPV1 mRNA and protein expressions were determined by quantitative polymerase chain reaction and semi-quantitative immunohistochemistry from the endometrium samples taken by curettage. Results were correlated with the clinical characteristics including pain intensity. TRPA1 and TRPV1 receptors were expressed in the healthy human endometrium at mRNA and protein levels. Sparse, scattered cytoplasmic TRPA1 and TRPV1 immunopositivities were found in the stroma and epithelial layers. We detected upregulated mRNA levels in deep infiltrating endometriosis lesions, and TRPV1 gene expression was also elevated in autocontrol endometrium of deep infiltrating endometriosis patients. Histological scoring revealed significant TRPA1 and TRPV1 difference between deep infiltrating endometriosis stroma and epithelium, and in deep infiltrating endometriosis epithelium compared to control samples. Besides, we measured elevated stromal TRPV1 immunopositivity in deep infiltrating endometriosis. Stromal TRPA1 and TRPV1 immunoreactivities strongly correlated with dysmenorrhoea severity, as well TRPV1 expression on ectopic epithelial cells and macrophages with dyspareunia. Epithelial TRPA1 and stromal TRPV1 immunopositivity also positively correlated with dyschezia severity. We provide the first evidence for the presence of non-neuronal TRPA1 receptor in the healthy human endometrium and confirm the expression of TRPV1 channels. Their upregulations in rectosigmoid deep infiltrating endometriosis lesions and correlations with pain intensity suggest potential roles in pathophysiological mechanisms of the disease.