Genistein regulates the IL-1 beta induced activation of MAPKs in human periodontal ligament cells through G protein-coupled receptor 30

Luo, Lijun; Liu, Feng; Lin, Zhikai; Xie, Yufeng; Xu, Jiali; Tong, Qingchun; Shu, Rong

doi:10.1016/j.abb.2012.04.007

Cited by 46 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, previously published data also indicated a possible implication of GPR30 in the inflammatory processes in the GI tract. Luo et al found that the GPR30 expression in human periodontal ligament (PDL) cells is regulated by IL-1β [19]. They also demonstrated that an increase in GPR30 level in human PDL cells leads to the activation of multiple signaling pathways, including MAPK, NF-κB and PI3K dependent.…”

Section: Discussionmentioning

confidence: 99%

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

Włodarczyk

Sobolewska-Włodarczyk

Cygankiewicz

et al. 2020

JGLD

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Włodarczyk

Sobolewska-Włodarczyk

Cygankiewicz

et al. 2020

JGLD

View full text Add to dashboard Cite

show abstract

“…Such properties include actions upon peroxisome proliferator-activated receptor isoforms, estrogen receptors, tyrosine kinases, DNA topoisomerase II, and NF-κB activation [61–63]. There are a few reports about regulation of GPCRs by isoflavones, although most describe effects on estrogen receptor 1 (GPER1/GPR30) [64, 65]. …”

Section: Discussionmentioning

confidence: 99%

Antagonism of human formyl peptide receptor 1 (FPR1) by chromones and related isoflavones

Schepetkin

Kirpotina

Khlebnikov

et al. 2014

Biochemical Pharmacology

View full text Add to dashboard Cite

Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) expressed on a variety of cell types. Because FPRs play an important role in the regulation of inflammatory reactions implicated in disease pathogenesis, FPR antagonists may represent novel therapeutics for modulating innate immunity. Previously, 4H-chromones were reported to be potent and competitive FPR1 antagonists. In the present studies, 96 additional chromone analogs, including related synthetic and natural isoflavones were evaluated for FPR1 antagonist activity. We identified a number of novel competitive FPR1 antagonists that inhibited fMLF-induced intracellular Ca2+ mobilization in FPR1-HL60 cells and effectively competed with WKYMVm-FITC for binding to FPR1 in FPR1-HL60 and FPR1-RBL cells. Compound 10 (6-hexyl-2-methyl-3-(1-methyl-1H-benzimidazol-2-yl)-4-oxo-4H-chromen-7-yl acetate) was found to be the most potent FPR1-specific antagonist, with binding affinity Ki~100 nM. These chromones inhibited Ca2+ flux and chemotaxis in human neutrophils with nanomolar-micromolar IC50 values. In addition, the most potent novel FPR1 antagonists inhibited fMLF-induced phosphorylation of extracellular signal-regulated kinases (ERK1/2) in FPR1-RBL cells. These antagonists were specific for FPR1 and did not inhibit WKYMVM/WKYMVm-induced intracellular Ca2+ mobilization in FPR2-HL60 cells, FPR3-HL60 cells, RBL cells transfected with murine Fpr1, or interleukin 8-induced Ca2+ flux in human neutrophils and RBL cells transfected with CXC chemokine receptor 1 (CXCR1). Moreover, pharmacophore modeling showed that the active chromones had a significantly higher degree of similarity with the pharmacophore template as compared to inactive analogs. Thus, the chromone/isoflavone scaffold represents a relevant backbone for development of novel FPR1 antagonists.

show abstract

“…Previous researches showed that GPER regulated the activities of epidermal growth factor receptors (EGFRs), mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathways [41, 42]. In this study, we conducted a microarray to explore the upstream regulator of AR.…”

Section: Discussionmentioning

confidence: 99%

The Androgen Receptor Promotes Cellular Proliferation by Suppression of G-Protein Coupled Estrogen Receptor Signaling in Triple-Negative Breast Cancer

Shen

Yang

Zhang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The targeted therapy for triple-negative breast cancer (TNBC) is still challenging due to poor understanding on its molecular etiology. The androgen receptor (AR) has recently emerged as a prognostic and treatment-predictive marker in breast cancer. However, the role of AR in TNBC remained elusive. Methods: Immunohistochemistry (IHC) was used to detect AR and G-protein coupled estrogen receptor (GPER) expression in tissue microarrays of 165 TNBC patients. Microarray analysis of mRNAs was performed to identify downstream regulators of AR. TNBC cells were cultured with dihydrotestosterone (DHT) alone or in combination with AR knockdown performed with AR shRNA. Cell viability and colony formation were assessed. Western blotting and qRT-PCR were used to examine protein and mRNA expression, respectively. The potential mechanism of AR-mediated GPER suppression was identified by Chromatin immunoprecipitation (ChIP) assay. AR and GPER expressions were also assessed in nude mouse xenografts by IHC. Results: IHC staining showed that the expression of AR was positively associated with tumor size, lymph node metastasis and high-grade tumor in TNBC patients. AR activation triggered by DHT suppressed GPER expression, to promote cell growth of TNBC. G-1, a GPER agonist, inhibited DHT-stimulated proliferation. Further experiments illustrated that AR suppressed GPER activation via binding directly to the promoter of GPER. Moreover, a negative correlation between AR and GPER was observed in MDA-MB-231 tumor cell xenografts and TNBC patient samples. Conclusions: The suppression of GPER via AR may be involved in the positive actions towards the TNBC progression, making it a promising therapeutic target for TNBC treatment.

show abstract

Genistein regulates the IL-1 beta induced activation of MAPKs in human periodontal ligament cells through G protein-coupled receptor 30

Cited by 46 publications

References 30 publications

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

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

Antagonism of human formyl peptide receptor 1 (FPR1) by chromones and related isoflavones

The Androgen Receptor Promotes Cellular Proliferation by Suppression of G-Protein Coupled Estrogen Receptor Signaling in Triple-Negative Breast Cancer

Contact Info

Product

Resources

About