G Protein-Coupled Receptor 30 (GPR30) Expression Pattern in Inflammatory Bowel Disease Patients Suggests its Key Role in the Inflammatory Process. A Preliminary Study

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.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.

Periodontitis and inflammatory bowel disease: a meta-analysis

“…The level of TNF-α is elevated in the gastrointestinal tract of CD patients, as well as in the gingival crevicular fluid of periodontitis patients. GPR30 mRNA and protein expression were detectable in the colonic tissues of IBD patients and may play a role in the intestinal inflammatory balance [36].…”

“…Another linkage between periodontitis and IBD is related to immune-inflammatory response. Specifically, a possible role for G proteincoupled receptor 30 (GPR30) and tumor necrosis factorα (TNF-α) has been implicated [35][36][37][38]. The level of TNF-α is elevated in the gastrointestinal tract of CD patients, as well as in the gingival crevicular fluid of periodontitis patients.…”

G Protein-Coupled Estrogen Receptor in Immune Cells and Its Role in Immune-Related Diseases

“…Interestingly, GPER1 seems to play a significant role in large bowel physiology and disease [see ( 12 ) for a review]. More specifically, GPER1 seems to be downregulated in Inflammatory Bowel Disease and especially Crohn’s disease, as compared to the normal tissue, suggestive of a protective role of the receptor in bowel inflammation ( 81 ). Although the data are not conclusive, the fact that GPER1 is expressed preferentially in normal tissue ( 81 ), together with its anti-inflammatory effect on different lineages of circulating or tissue-resident immune cells, as discussed above ( 28 , 31 – 33 , 35 , 44 ), suggest a potential role of this receptor in bowel inflammation, a condition that when is present for prolonged periods of time (chronic colonic inflammation) is a risk factor for colon carcinogenesis ( 12 ).…”

Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner

“…The threshold cycle (Ct) values for studied genes were normalized to Ct values obtained for a housekeeping gene, Hprt1. The relative expression levels were normalized to Hprt1 and calculated as 2^[− (Ct FABP4 − Ct HPRT1 )] × 1000 [33].…”