G蛋白偶联受体30(GPR30)在炎症性肠病患者中的表达模式表明其在炎症过程中的关键作用。一项初步研究。
G Protein-Coupled Receptor 30 (GPR30) Expression Pattern in Inflammatory Bowel Disease Patients Suggests its Key Role in the Inflammatory Process. A Preliminary Study.
作者信息
Włodarczyk Marcin, Sobolewska-Włodarczyk Aleksandra, Cygankiewicz Adam I, Jacenik Damian, Piechota-Polańczyk Aleksandra, Stec-Michalska Krystyna, Krajewska Wanda M, Fichna Jakub, Wiśniewska-Jarosińska Maria
机构信息
Department of Biochemistry, Medical University of Lodz, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Department of Biochemistry, Medical University of Lodz;Department of Gastroenterology,Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
出版信息
J Gastrointestin Liver Dis. 2017 Mar;26(1):29-35. doi: 10.15403/jgld.2014.1121.261.gpr.
BACKGROUND AND AIMS
G protein-coupled receptor 30 (GPR30) is a recently de-orphanized estrogen receptor that mediates the effects of estrogens on different cells. It has been postulated that in inflammatory bowel diseases (IBD) activation of GPR30 blocks the pathways dependent on pro-inflammatory cytokines. The aim of our study was to investigate GPR30 expression in patients with IBD and its potential implication in future therapies.
METHODS
Fifty-seven patients were enrolled in our study: 20 subjects with Crohn's disease (CD), 22 with ulcerative colitis (UC) and 15 controls. In each subject, biopsies were taken from various left-colonic locations. Gene and protein expression of GPR30 was quantified using real time RT-PCR or Western blot.
RESULTS
GPR30 mRNA and protein expression were detected in all tested colonic tissues. No significant differences in GPR30 gene expression were observed. In non-inflamed areas, GPR30 protein was strongly increased in CD patients, but moderately in UC patients (p= 0.014 and p=0.143, respectively, vs. controls). In CD patients, a significantly lower GPR30 protein content in inflamed than in non-inflamed tissue was observed (p=0.039). The change was independent of patient gender.
CONCLUSION
Our observations indicate that GPR30 may play a role in the development and progression of inflammatory lesions in IBD, thus affecting disease severity, and consequently IBD treatment. Therefore, GPR30 may become an attractive target for novel anti-IBD drugs, particularly in CD.
背景与目的
G蛋白偶联受体30(GPR30)是一种最近才明确功能的雌激素受体,可介导雌激素对不同细胞的作用。据推测,在炎症性肠病(IBD)中,GPR30的激活可阻断依赖促炎细胞因子的信号通路。我们研究的目的是调查IBD患者中GPR30的表达情况及其在未来治疗中的潜在意义。
方法
57名患者参与了我们的研究:20名克罗恩病(CD)患者、22名溃疡性结肠炎(UC)患者和15名对照者。在每个受试者中,从左半结肠的不同位置采集活检组织。使用实时逆转录聚合酶链反应(RT-PCR)或蛋白质免疫印迹法(Western blot)对GPR30的基因和蛋白表达进行定量分析。
结果
在所有检测的结肠组织中均检测到GPR30的信使核糖核酸(mRNA)和蛋白表达。未观察到GPR30基因表达的显著差异。在非炎症区域,CD患者的GPR30蛋白显著增加,而UC患者中度增加(分别与对照组相比,p = 0.014和p = 0.143)。在CD患者中,观察到炎症组织中的GPR30蛋白含量明显低于非炎症组织(p = 0.039)。这种变化与患者性别无关。
结论
我们的观察结果表明,GPR30可能在IBD炎症病变的发生和发展中起作用,从而影响疾病严重程度,进而影响IBD的治疗。因此,GPR30可能成为新型抗IBD药物的一个有吸引力的靶点,尤其是在CD中。