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https://www.readbyqxmd.com/read/28524744/sphingosine-1-phosphate-signaling-in-bone-remodeling-multifaceted-roles-and-therapeutic-potential
#1
Anastasia Meshcheryakova, Diana Mechtcheriakova, Peter Pietschmann
Sphingolipids belong to a complex class of lipid molecules that are crucially involved in the regulation of important biological processes including proliferation, migration and apoptosis. Given the significant progress made in understanding the sphingolipid pathobiology of several diseases, sphingolipid-related checkpoints emerge as attractive targets. Recent data indicate the multifaceted contribution of the sphingolipid machinery to osteoclast - osteoblast crosstalk, representing one of the pivotal interactions underlying bone homeostasis...
May 19, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28493876/the-effect-of-sphingosine-1-phosphate-on-colonic-smooth-muscle-contractility-modulation-by-tnbs-induced-colitis
#2
Aishah Al-Jarallah, Mabayoje Oriowo
AIM: Increased levels of circulating sphingosine-1-phosphate (S1P) have been reported in ulcerative colitis. The objective of this study was to examine the effect of S1P on colonic smooth muscle contractility and how is it affected by colitis. METHODS: Colonic inflammation was induced by intrarectal administration of trinitrobenzene sulfonic acid. Five days later colon segments were isolated and used for contractility experiments and immunoblotting. RESULTS: S1P contracted control and inflamed colon segments and the contraction was significantly greater in inflamed colon segments...
2017: PloS One
https://www.readbyqxmd.com/read/28492873/sphingosine-1-phosphate-mediates-fibrosis-in-orbital-fibroblasts-in-graves-orbitopathy
#3
JaeSang Ko, Min Kyoung Chae, Joon H Lee, Eun Jig Lee, Jin Sook Yoon
Purpose: To investigate the effect of sphingosine-1-phosphate (S1P) on fibrosis in orbital fibroblasts in Graves' orbitopathy (GO). Methods: Orbital fibroblasts were cultured from orbital adipose/connective tissues of patients with GO and healthy control subjects. Effects of treatment with TGF-β and cigarette smoke extract (CSE) on S1P receptor (S1PR) messenger RNA (mRNA) and S1P expression were evaluated by real-time polymerase chain reaction and Western blotting...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28400772/sphingolipids-are-dual-specific-drug-targets-for-the-management-of-pulmonary-infections-perspective
#4
REVIEW
Lalita Sharma, Hridayesh Prakash
Sphingolipids are the major constituent of the mucus secreted by the cells of epithelial linings of lungs where they maintain the barrier functions and prevent microbial invasion. Sphingolipids are interconvertible, and their primary and secondary metabolites have both structural and functional roles. Out of several sphingolipid metabolites, sphingosine-1 phosphate (S1P) and ceramide are central molecules and decisive for sphingolipid signaling. These are produced by enzymatic activity of sphingosine kinase-1 (SK-1) upon the challenge with either biological or physiological stresses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28302479/mir-126-impairs-the-intestinal-barrier-function-via-inhibiting-s1pr2-mediated-activation-of-pi3k-akt-signaling-pathway
#5
Tanzhou Chen, Haibo Xue, Ruoyang Lin, Zhiming Huang
BACKGROUND: Aberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD. METHODS: In this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2...
March 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28271527/the-role-of-lncrna-h19-in-gender-disparity-of-cholestatic-liver-injury-in-mdr2-mice
#6
Xiaojiaoyang Li, Runping Liu, Jing Yang, Lixin Sun, Luyong Zhang, Zhenzhou Jiang, Puneet Puri, Emily C Gurley, Guanhua Lai, Yuping Tang, Zhiming Huang, William M Pandak, Phillip B Hylemon, Huiping Zhou
The multi-drug resistance 2 knockout (Mdr2(-/-) ) mouse is a well-established model of cholestatic cholangiopathies. Female Mdr2(-/-) mice develop more severe hepatobiliary damage than male Mdr2(-/-) mice, which is correlated with a higher proportion of taurocholate (TCA) in bile. Although estrogen has been identified as an important player in intrahepatic cholestasis, the underlying molecular mechanisms of gender-based disparity of cholestatic injury remain unclear. The long non-coding RNA H19 is an imprinted, maternally expressed and estrogen-targeted gene, which is significantly induced in human fibrotic/cirrhotic liver and bile duct ligated mouse liver...
March 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28248965/pancreas-lineage-allocation-and-specification-are-regulated-by-sphingosine-1-phosphate-signalling
#7
Ioannis Serafimidis, Eva Rodriguez-Aznar, Mathias Lesche, Kazuaki Yoshioka, Yoh Takuwa, Andreas Dahl, Duojia Pan, Anthony Gavalas
During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated...
March 2017: PLoS Biology
https://www.readbyqxmd.com/read/28181168/apoa-i-sr-bi-modulates-s1p-s1pr2-mediated-inflammation-through-the-pi3k-akt-signaling-pathway-in-huvecs
#8
Kun Ren, Yan-Ju Lu, Zhong-Cheng Mo, Xing -Liu, Zhen-Li Tang, Yue Jiang, Xiao-Shan Peng, Li Li, Qing-Hai Zhang, Guang-Hui Yi
Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway...
February 8, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28143955/the-eph-related-tyrosine-kinase-ligand-ephrin-b1-marks-germinal-center-and-memory-precursor-b-cells
#9
Brian J Laidlaw, Timothy H Schmidt, Jesse A Green, Christopher D C Allen, Takaharu Okada, Jason G Cyster
Identification of germinal center (GC) B cells is typically reliant on the use of surface activation markers that exhibit a wide range of expression. Here, we identify Ephrin-B1, a ligand for Eph-related receptor tyrosine kinases, as a specific marker of mature GC B cells. The number of Ephrin-B1(+) GC B cells increases during the course of an immune response with Ephrin-B1(+) GC B cells displaying elevated levels of Bcl6, S1pr2, and Aicda relative to their Ephrin-B1(-) counterparts. We further identified a small proportion of recently dividing, somatically mutated Ephrin-B1(+) GC B cells that have begun to down-regulate Bcl6 and S1pr2 and express markers associated with memory B cells, such as CD38 and EBI2...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28120434/the-role-of-s1pr2-in-bile-acid-induced-cholangiocyte-proliferation-and-cholestasis-induced-liver-injury-in-mice
#10
Yongqing Wang, Hiroaki Aoki, Jing Yang, Kesong Peng, Runping Liu, Xiaojiaoyang Li, Xiaoyan Qiang, Lixin Sun, Emily C Gurley, Guanhua Lai, Luyong Zhang, Guang Liang, Masayuki Nagahashi, Kazuaki Takabe, William M Pandak, Phillip B Hylemon, Huiping Zhou
Bile duct obstruction is a potent stimulus for cholangiocyte proliferation, especially for large cholangiocytes. Our previous studies reported that conjugated bile acids (CBAs) activate the AKT and ERK1/2 signaling pathways via the sphingosine 1-phosphate receptor 2 (S1PR2) in hepatocytes and cholangiocarcinoma cells. It also has been reported that taurocholate (TCA) promotes large cholangiocyte proliferation and protects cholangiocytes from bile duct ligation (BDL)-induced apoptosis. However, the role of S1PR2 in bile acid-mediated cholangiocyte proliferation and cholestatic liver injury has not been elucidated...
January 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27994962/regulation-of-s1p-receptors-and-sphingosine-kinases-expression-in-acute-pulmonary-endothelial-cell-injury
#11
Huiying Liu, Zili Zhang, Puyuan Li, Xin Yuan, Jing Zheng, Jinwen Liu, Changqing Bai, Wenkai Niu
BACKGROUND: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30-40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function...
2016: PeerJ
https://www.readbyqxmd.com/read/27959929/histological-transformation-and-progression-in-follicular-lymphoma-a-clonal-evolution-study
#12
Robert Kridel, Fong Chun Chan, Anja Mottok, Merrill Boyle, Pedro Farinha, King Tan, Barbara Meissner, Ali Bashashati, Andrew McPherson, Andrew Roth, Karey Shumansky, Damian Yap, Susana Ben-Neriah, Jamie Rosner, Maia A Smith, Cydney Nielsen, Eva Giné, Adele Telenius, Daisuke Ennishi, Andrew Mungall, Richard Moore, Ryan D Morin, Nathalie A Johnson, Laurie H Sehn, Thomas Tousseyn, Ahmet Dogan, Joseph M Connors, David W Scott, Christian Steidl, Marco A Marra, Randy D Gascoyne, Sohrab P Shah
BACKGROUND: Follicular lymphoma (FL) is an indolent, yet incurable B cell malignancy. A subset of patients experience an increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immunochemotherapy. The nature of tumor clonal dynamics leading to these clinical end points is poorly understood, and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27829417/administration-of-jte013-abrogates-experimental-asthma-by-regulating-proinflammatory-cytokine-production-from-bronchial-epithelial-cells
#13
Tomomi Terashita, Kazuyuki Kobayashi, Tatsuya Nagano, Yoshitaka Kawa, Daisuke Tamura, Kyosuke Nakata, Masatsugu Yamamoto, Motoko Tachihara, Hiroshi Kamiryo, Yoshihiro Nishimura
BACKGROUND: Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that acts as a signal transducer by binding to S1P receptors (S1PR) 1 to 5. The S1P/S1PRs pathway has been associated with remodeling and allergic inflammation in asthma, but the expression pattern of S1PR and its effects on non-immune cells have not been completely clarified. The aim of this study was to examine the contribution of the signaling of S1P and S1PRs expressed in airway epithelial cells (ECs) to asthma responses in mice...
November 9, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27814635/sphingosine-1-phosphate-promotes-intestinal-epithelial-cell-proliferation-via-s1pr2
#14
Tanzhou Chen, Zhiming Huang, Runping Liu, Jing Yang, Phillip B Hylemon, Huiping Zhou
Sphingosine-1 phosphate (S1P) is a potent bioactive lipid mediator that acts both as an intracellular signaling molecule and a natural ligand of five different G protein-coupled receptors (GPCRs), S1PR1-5. The level of S1P in intestinal tissue is abundant. Previous studies have reported that S1P protects intestinal epithelial cell from apoptosis by activating the ERK and Akt signaling pathways. However, the effect of S1P on intestinal epithelial cell proliferation under physiological conditions and the underlying signaling mechanisms remain to be elucidated...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27801960/inhibition-of-the-sphk1-s1p-signaling-pathway-by-melatonin-in-mice-with-liver-fibrosis-and-human-hepatic-stellate-cells
#15
Bárbara González-Fernández, Diana I Sánchez, Irene Crespo, Beatriz San-Miguel, Marcelino Álvarez, María J Tuñón, Javier González-Gallego
The sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) system is involved in different pathological processes, including fibrogenesis. Melatonin abrogates activation of hepatic stellate cells (HSCs) and attenuates different profibrogenic pathways in animal models of fibrosis, but it is unknown if protection associates with its inhibitory effect on the SphK1/S1P axis. Mice in treatment groups received carbon tetrachloride (CCl4 ) 5 μL g(-1) body wt i.p. twice a week for 4 or 6 weeks. Melatonin was given at 5 or 10 mg kg(-1)  day(-1) i...
March 2017: BioFactors
https://www.readbyqxmd.com/read/27696512/melatonin-prevents-deregulation-of-the-sphingosine-kinase-sphingosine-1-phosphate-signaling-pathway-in-a-mouse-model-of-diethylnitrosamine-induced-hepatocellular-carcinoma
#16
Diana I Sánchez, Bárbara González-Fernández, Beatriz San-Miguel, Juan Ortiz de Urbina, Irene Crespo, Javier González-Gallego, María J Tuñón
The sphingosine kinase (SphK)/sphingosine 1-phosphate (S1P) pathway is involved in multiple biological processes, including carcinogenesis. Melatonin shows beneficial effects in cell and animal models of hepatocellular carcinoma, but it is unknown if they are associated with the modulation of the SphK/S1P system, along with different downstream signaling pathways modified in cancer. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p) once a week for 8 weeks...
January 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/27612439/sphingosine-1-phosphate-s1pr2-mediated-signaling-triggers-smad1-5-8-phosphorylation-and-thereby-induces-runx2-expression-in-osteoblasts
#17
Katsumasa Higashi, Etsuko Matsuzaki, Yoko Hashimoto, Fumi Takahashi-Yanaga, Aiko Takano, Hisashi Anan, Masato Hirata, Fusanori Nishimura
Sphingosine-1-phosphate (S1P) is a signaling sphingolipid that also plays crucial roles in bone regeneration. Recently, we reported that the S1P receptors S1PR1 and S1PR2 were mainly expressed in osteoblast-like cells, and that the S1P/S1PR1 signaling pathway up-regulated osteoprotegerin and osteoblast differentiation. However, the involvement of S1P/S1PR2 signaling in osteoblast differentiation is not well understood. Here we investigate the role of S1P/S1PR2-mediated signaling in osteoblast differentiation and clarify the underlying signaling mechanisms...
September 6, 2016: Bone
https://www.readbyqxmd.com/read/27611089/the-neurite-outgrowth-inhibitory-nogo-a-%C3%AE-20-region-is-an-intrinsically-disordered-segment-harbouring-three-stretches-with-helical-propensity
#18
Viviane Zelenay, Michael E Arzt, Stefan Bibow, Martin E Schwab, Roland Riek
Functional recovery from central neurotrauma, such as spinal cord injury, is limited by myelin-associated inhibitory proteins. The most prominent example, Nogo-A, imposes an inhibitory cue for nerve fibre growth via two independent domains: Nogo-A-Δ20 (residues 544-725 of the rat Nogo-A sequence) and Nogo-66 (residues 1026-1091). Inhibitory signalling from these domains causes a collapse of the neuronal growth cone via individual receptor complexes, centred around sphingosine 1-phosphate receptor 2 (S1PR2) for Nogo-A-Δ20 and Nogo receptor 1 (NgR1) for Nogo-66...
2016: PloS One
https://www.readbyqxmd.com/read/27501354/fty720p-inhibits-hepatic-na-k-atpase-via-s1pr2-and-pge2
#19
Nadine Al Alam, Sawsan Ibrahim Kreydiyyeh
Sphingosine-1-phosphate (S1P) was found previously to inhibit Na(+)-K(+) ATPase in HepG2 cells. Whether fingolimod (FTY720), a S1P receptor (S1PR) agonist, similarly inhibits the ATPase is a question that needs to be addressed. The aim of this work was to study the effect of FTY720P, the active form of the drug, on the activity of Na(+)-K(+) ATPase in HepG2 cells and determine its mechanism of action. The activity of the ATPase was assayed by measuring the amount of inorganic phosphate liberated in the presence and the absence of ouabain...
August 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/27459945/the-roles-of-bile-acids-and-sphingosine-1-phosphate-signaling-in-the-hepatobiliary-diseases
#20
REVIEW
Masayuki Nagahashi, Kizuki Yuza, Yuki Hirose, Masato Nakajima, Rajesh Ramanathan, Nitai C Hait, Phillip B Hylemon, Huiping Zhou, Kazuaki Takabe, Toshifumi Wakai
Based on research carried out over the last decade, it has become increasingly evident that bile acids act not only as detergents, but also as important signaling molecules that exert various biological effects via activation of specific nuclear receptors and cell signaling pathways. Bile acids also regulate the expression of numerous genes encoding enzymes and proteins involved in the synthesis and metabolism of bile acids, glucose, fatty acids, and lipoproteins, as well as energy metabolism. Receptors activated by bile acids include, farnesoid X receptor α, pregnane X receptor, vitamin D receptor, and G protein-coupled receptors, TGR5, muscarinic receptor 2, and sphingosine-1-phosphate receptor (S1PR)2...
September 2016: Journal of Lipid Research
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