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Search results for: G Protein Coupled Receptor GPR174 JEG18, Human

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#32894510   // To Up

Druggable Lysophospholipid Signaling Pathways.

Lysophosphatidic acid (LPA) has major roles as a bioactive signaling molecule, with multiple physiological and pathological roles being described in almost every major organ system. In this review we discuss LPA signaling pathways as emerging drug targets for multiple conditions relevant to human health and disease. LPA signals through the six G protein-coupled receptors LPA, and several of these receptors along with the LPA-producing enzyme including autotaxin (ATX) are now established as therapeutic targets with potential to treat various human diseases as exemplified by several LPA signaling targeting compounds now in clinical trials for idiopathic pulmonary fibrosis and systemic sclerosis. Several crystal structures of LPA receptors and ATX have been solved, which will accelerate development of highly selective and effective LPA signaling targeting compounds. We also review additional bioactive lysophospholipid (LPL) signaling molecules including lysophosphatidylserine and lysophosphatidylinositol, which represent the next wave of LPL druggable targets. An emerging theme in bioactive LPL signaling is that where the ligand is produced and how it is delivered to the cognate receptor are critical determinants of the biological responses. We will also discuss how connecting the production and function of bioactive LPLs will identify new therapeutic strategies to effectively target LPL signaling pathways.
Keisuke Yanagida, William J Valentine

1570 related Products with: Druggable Lysophospholipid Signaling Pathways.

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#32727090   2020/07/27 To Up

GPR174 and ITM2A Gene Polymorphisms rs3827440 and rs5912838 on the X chromosome in Korean Children with Autoimmune Thyroid Disease.

(1) Background: Autoimmune thyroid diseases (AITDs) are female predominant and much attention has been focused on G protein-coupled receptor 174 ( and integral membrane protein 2A ( on the X chromosome as Grave's disease (GD) susceptible locus. (2) Methods: We genotyped four single nucleotide polymorphisms (SNPs), rs3810712, rs3810711, rs3827440, and rs5912838, of and in 115 Korean children with AITD (M = 25 and F = 90; GD = 74 (14.7 ± 3.6 years), HD = 41 (13.4 ± 3.2 years); GD-thyroid-associated ophthalmopathy (TAO) = 40, GD-non-TAO=34) and 204 healthy Korean individuals (M = 104 and F = 100). The data were analyzed by sex-stratified or combined. (3) Results: Three SNPs, rs3810712, rs3810711 and rs3827440, were found to be in perfect linkage disequilibrium (' = 1, r = 1). In AITD, HD, GD, GD-TAO, and GD-non-TAO patients, rs3827440 TT/T and rs5912838 AA/A were susceptible and rs3827440 CC/C and rs5912838 CC/C were protective genotypes. When analyzed by sex, rs3827440 TT and rs5912838 AA were susceptible and rs3827440 CC and rs5912838 CC were protective genotypes in female AITD, GD, GD-TAO, and GD-non-TAO subjects. In male AITD patients, rs3827440 T and rs5912838 A were susceptible and rs3827440 C and rs5912838 C were protective genotypes. (4) Conclusions: Polymorphisms in and genes on the X chromosome might be associated with AITD in Korean children.
Won Kyoung Cho, Hye-Ri Shin, Na Yeong Lee, Seul Ki Kim, Moon Bae Ahn, In-Cheol Baek, Tai-Gyu Kim, Byung-Kyu Suh

1010 related Products with: GPR174 and ITM2A Gene Polymorphisms rs3827440 and rs5912838 on the X chromosome in Korean Children with Autoimmune Thyroid Disease.

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#32342657   2020/04/27 To Up

Candidate gene associations reveal sex-specific Graves' disease risk alleles among Chinese Han populations.

With several susceptibility single nucleotide polymorphisms identified by case-control association studies, Graves' disease is one of the most common forms of autoimmune thyroid disease. In this study, we aimed to determine whether any observed differences in genetic associations are influenced by sex in Chinese Han populations.
Chen-Yan Yan, Yu-Ru Ma, Feng Sun, Rui-Jia Zhang, Ya Fang, Qian-Yue Zhang, Feng-Yao Wu, Shuang-Xia Zhao, Huai-Dong Song

1961 related Products with: Candidate gene associations reveal sex-specific Graves' disease risk alleles among Chinese Han populations.

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#32246145   // To Up

Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves' Disease and Hashimoto's Hypothyroidism.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the 2 main autoimmune thyroid diseases that have both similarities and differences. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these closely related diseases.
Qian-Yue Zhang, Wei Liu, Lu Li, Wen-Hua Du, Chun-Lin Zuo, Xiao-Ping Ye, Zheng Zhou, Fei-Fei Yuan, Yu-Ru Ma, Feng Sun, Sha-Sha Yu, Hui-Jun Xie, Chang-Run Zhang, Ying-Xia Ying, Guo-Yue Yuan, Guan-Qi Gao, Jun Liang, Shuang-Xia Zhao, Huai-Dong Song

2293 related Products with: Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves' Disease and Hashimoto's Hypothyroidism.

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#31786099   2019/11/27 To Up

The increased marginal zone B cells attenuates early inflammatory responses during sepsis in Gpr174 deficient mice.

GPR174 plays a crucial role in immune responses, but the role of GPR174 in the pathological progress of sepsis remains incompletely understood. In this study, we generated a sepsis model by cecal ligation and puncture (CLP) to investigate the role of GPR174 in regulating functions and underlying mechanism of marginal zone B (MZ B) cells in sepsis. We found that in Gpr174 deficient mice, the number of splenic MZ B cells was increased. Moreover, Gpr174 MZ B cells exhibited an enhanced response to LPS stimulation in vitro. By using the CLP-induced sepsis model, we demonstrated that the increased MZ B cells attenuated early inflammatory responses during sepsis. RNA sequencing results revealed that the expression of c-fos in splenic B lymphocytes was upregulated in Gpr174 deficient mice. However, the protective role of increased MZ B cells in Gpr174 deficient mice was weakened by a c-fos-specific inhibitor. Collectively, these findings suggested that GPR174 plays an immunomodulatory role in early immune responses during sepsis through the regulation of MZ B cells.
Ming Zhu, Chong Li, Zhenju Song, Sucheng Mu, Jianli Wang, Wei Wei, Yi Han, Dongze Qiu, Xun Chu, Chaoyang Tong

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#30850582   2019/03/08 To Up

Gpr174-deficient regulatory T cells decrease cytokine storm in septic mice.

G protein-coupled receptor 174 (GPR174) is mainly expressed in thymus, spleen, lymph nodes, and leukocytes, and genetic variation in GPR174 is associated with susceptibility to autoimmune diseases, indicating that GPR174 is involved in the immune response. However, the function of GPR174 in regulating inflammatory responses against bacterial infection in sepsis remains unclear. In this study, we investigated the role of GPR174 in regulating suppressive function of regulatory T cells (Treg cells) and the underlying mechanism of Gpr174-deficient Treg cells in controlling cytokine storm of sepsis. We showed that Gpr174-dedicient mice were resistant to inflammatory shock induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP). Moreover, Gpr174 was highly expressed in Treg cells, and its deficiency in mice promoted the expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and interleukin (IL)-10 in Treg cells. By using the LPS-induced sepsis model, we demonstrated that anti-inflammatory macrophages (M2 macrophages) induction was Treg cell-dependent and Gpr174-deficient Treg cells protected mice against sepsis-induced lung damage through prompting M2 macrophages polarization. In vitro, Gpr174-deficient Treg cells also promoted the polarization of macrophages toward M2 cells and dampened the secretions of pro-inflammatory cytokines (IL-6 and tumor necrosis factor-α (TNF-α)) in macrophages. In conclusion, these findings suggested that GPR174 plays an important role in the initial period of sepsis through the regulation of macrophage polarization and pro- and anti-inflammatory cytokine secretions. Therefore, GPR174 may be a promising target for therapeutic agents to regulate inflammatory disorders.
Dongze Qiu, Xun Chu, Laiqing Hua, Yunke Yang, Keyong Li, Yi Han, Jun Yin, Ming Zhu, Sucheng Mu, Zhan Sun, Chaoyang Tong, Zhenju Song

1020 related Products with: Gpr174-deficient regulatory T cells decrease cytokine storm in septic mice.

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#29700886   2018/05/24 To Up

Lysophosphatidylserine receptor P2Y10: A G protein-coupled receptor that mediates eosinophil degranulation.

P2Y10, along with GPR34 and GPR174, is a G protein-coupled receptor that is activated by an endogenous lipid mediator lysophosphatidylserine (LysoPS). Its expression pattern and its function are completely unknown. We have previously shown that P2Y10 is one of the highly up-regulated genes at the late differentiation stage during in vitro eosinophilopoiesis.
S M Hwang, H J Kim, S M Kim, Y Jung, S W Park, I Y Chung

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#28568286   2017/05/31 To Up

RNASET2, GPR174, and PTPN22 gene polymorphisms are related to the risk of liver damage associated with the hyperthyroidism in patients with Graves' disease.

This study was designed to unveil the association of GPR174 rs3827440, PTPN22 rs3789604, and RNASET2 rs9355610 with the onset of liver damage (LD) among the Graves' disease (GD) patients.
Qing Zhang, Shaozheng Liu, Yanxing Guan, Qingjie Chen, Qing Zhang, Xiang Min

1633 related Products with: RNASET2, GPR174, and PTPN22 gene polymorphisms are related to the risk of liver damage associated with the hyperthyroidism in patients with Graves' disease.

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#27077565   2016/04/14 To Up

Conformational Constraint of the Glycerol Moiety of Lysophosphatidylserine Affords Compounds with Receptor Subtype Selectivity.

Lysophosphatidylserine (LysoPS) is an endogenous lipid mediator that specifically activates membrane proteins of the P2Y and its related families of G protein-coupled receptors (GPCR), GPR34 (LPS1), P2Y10 (LPS2), and GPR174 (LPS3). Here, in order to increase potency and receptor selectivity, we designed and synthesized LysoPS analogues containing the conformational constraints of the glycerol moiety. These reduced structural flexibility by fixation of the glycerol framework of LysoPS using a 2-hydroxymethyl-3-hydroxytetrahydropyran skeleton, and related structures identified compounds which exhibited high potency and selectivity for activation of GPR34 or P2Y10. Morphing of the structural shape of the 2-hydroxymethyl-3-hydroxytetrahydropyran skeleton into a planar benzene ring enhanced the P2Y10 activation potentcy rather than the GPR34 activation.
Sejin Jung, Asuka Inoue, Sho Nakamura, Takayuki Kishi, Akiharu Uwamizu, Misa Sayama, Masaya Ikubo, Yuko Otani, Kuniyuki Kano, Kumiko Makide, Junken Aoki, Tomohiko Ohwada

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