G Protein-Coupled Receptor 30 (GPR30) Expression Pattern in Inflammatory Bowel Disease Patients Suggests its Key Role in the Inflammatory Process. A Preliminary Study download Full Article (PDF file)
Marcin Włodarczyk1*, Aleksandra Sobolewska-Włodarczyk1,2*, Adam I. Cygankiewicz3, Damian Jacenik3, Aleksandra Piechota-Polańczyk2, Krystyna Stec-Michalska2, Wanda M. Krajewska3, Jakub Fichna1, Maria Wiśniewska-Jarosińska2
1) Department of Biochemistry, Medical University of Lodz,
2) Department of Gastroenterology, Medical University of Lodz,
3) Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
ABSTRACT Background & 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. Key words: GPR30 – inflammatory bowel diseases – Crohn’s disease – ulcerative colitis – biological therapy. Abbreviations: CRP: C-reactive protein; C-IBS: constipation-predominant IBS; CD: Crohn’s disease; D-IBS: diarrhea-predominant IBS; ER: Estrogen; GPER: G protein – coupled estrogen receptor 1; GPR30: G protein-coupled receptor 30; GI: gastrointestinal; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; IBD: inflammatory bowel diseases; IL: Interleukin; ICAM-1: intracellular cell adhesion molecule-1; IBS: irritable bowel syndrome; PDL: periodontal ligament; Th: T helper; TNF-α: tumor necrosis factor-α; UC: ulcerative colitis; VCAM-1: vascular cell adhesion molecule-1; WBC: white blood cells.