Qin Bin, Dong Lei, Guo Xiaoyan, Jiang Jiong, He Yangxin, Wang Xiaoyan, Li Lu, Zhao Juhui
Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):2238-46. eCollection 2014.
Estrogen is suggested to participate in pathogenesis of irritable bowel syndrome (IBS), but expression of G protein-coupled estrogen receptor (GPER) in the colon of IBS patients has never been investigated. The aim of this study was to investigate the expression of GPER and classical estrogen receptors in the colon of IBS patients and healthy controls.
Colonic biopsies were obtained by endoscopy from patients with IBS (n=46) and healthy subjects (n=13). Expression of GPER, estrogen receptor α (ERα) and estrogen receptor β (ERβ) in mast cells were measured by double-labelling immunofluorescence. Quantification of mRNA expression was performed for GPER, ERα and ERβ by real-time polymerase chain reaction.
Differential distribution of GPER, ERα and ERβ were detected in human colonic mucosa. The expression of GPER in the cytoplasm of mast cells and GPER-positive cells was significantly higher in diarrhea-predominant IBS (D-IBS) patients than that in constipation-predominant IBS (C-IBS, P<0.001) patients and healthy subjects (P=0.005). ERα and ERβ were not detected in majority of mast cells in colonic mucosa and no difference of immunostaining results for ERα and ERβ was found among these three groups. A positive correlation (r=0.451, P=0.011) between GPER-positive cell counts and abdominal pain severity was observed in D-IBS group. Relative mRNA expression of GPER in D-IBS was also higher than that in C-IBS (P=0.018) and healthy subjects (P=0.011).
The present study, for the first time, demonstrated the expression of GPER in human colonic mucosa and its correlation with abdominal pain severity.
雌激素被认为参与了肠易激综合征(IBS)的发病机制,但从未对IBS患者结肠中G蛋白偶联雌激素受体(GPER)的表达进行过研究。本研究的目的是调查IBS患者和健康对照者结肠中GPER及经典雌激素受体的表达情况。
通过内镜检查从IBS患者(n = 46)和健康受试者(n = 13)获取结肠活检组织。采用双标免疫荧光法检测肥大细胞中GPER、雌激素受体α(ERα)和雌激素受体β(ERβ)的表达。通过实时聚合酶链反应对GPER、ERα和ERβ的mRNA表达进行定量分析。
在人结肠黏膜中检测到GPER、ERα和ERβ的分布存在差异。腹泻型IBS(D-IBS)患者肥大细胞胞质及GPER阳性细胞中GPER的表达显著高于便秘型IBS(C-IBS,P < 0.001)患者和健康受试者(P = 0.005)。结肠黏膜中大多数肥大细胞未检测到ERα和ERβ,这三组之间ERα和ERβ的免疫染色结果无差异。在D-IBS组中观察到GPER阳性细胞计数与腹痛严重程度呈正相关(r = 0.451,P = 0.011)。D-IBS中GPER的相对mRNA表达也高于C-IBS(P = 0.018)和健康受试者(P = 0.011)。
本研究首次证明了GPER在人结肠黏膜中的表达及其与腹痛严重程度的相关性。