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https://www.readbyqxmd.com/read/28626422/sphingosine-1-phosphate-receptors-do-they-have-a-therapeutic-potential-in-cardiac-fibrosis
#1
REVIEW
Ambra Vestri, Federica Pierucci, Alessia Frati, Lucia Monaco, Elisabetta Meacci
Sphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors, which were initially named endothelial differentiation gene (Edg) and eventually renamed sphingosine 1-phosphate receptors (S1PRs). Among the five S1PR subtypes, S1PR1, S1PR2 and S1PR3 isoforms show broad tissue gene expression, while S1PR4 is primarily expressed in immune system cells, and S1PR5 is expressed in the central nervous system...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28598085/-inhibitory-effects-of-sphingosine-1-phosphate-receptor-2-on-vascular-permeability-in-mice
#2
Xiao-Wan Li, Xiu-Guo Li, Yoh Takuwa, Hong Cui
OBJECTIVES: To determine the effect of sphingosine-1-phosphate receptor 2 (S1PR2) on vascular permeability in mice. METHODS: Acute lung injury models of mice were constructed with intra-tracheal administration of lipopolysaccharide (LPS) and compared with the controls with intra-tracheal administration of saline. The effect of S1PR2 on vascular permeability was observed by detecting leakage of Evans blue into lung tissues, pulmonary vascular leakage of fluorescein isothiocyanate (FITC)-dextran, and the wet/dry mass ratio of lungs...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28596734/characterization-and-expression-of-sphingosine-1-phosphate-receptors-in-human-and-rat-heart
#3
Naseer Ahmed, Daniele Linardi, Ilaria Decimo, Riffat Mehboob, Mebratu A Gebrie, Giulio Innamorati, Giovanni B Luciani, Giuseppe Faggian, Alessio Rungatscher
Aim: Sphingosine 1-phosphate (S1P), sphingolipid derivatives are known anti-inflammatory, anti-apoptotic, and anti-oxidant agent. S1P have been demonstrated to have a role in the cardiovascular system. The purpose of this study was to understand the precise expression and distribution of S1P receptors (S1PRs) in human and rat cardiovascular tissues to know the significance and possible implementation of our experimental studies in rat models. Methods and Results: In this study, we investigated the localization of S1PRs in human heart samples from cardiac surgery department, University of Verona Hospital and rat samples...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28560734/substrate-properties-of-zebrafish-rtn4b-nogo-and-axon-regeneration-in-the-zebrafish-optic-nerve
#4
Vsevolod Bodrikov, Cornelia Welte, Marianne Wiechers, Markus Weschenfelder, Gurjot Kaur, Aleksandra Shypitsyna, Alejandro Pinzon-Olejua, Martin Bastmeyer, Claudia A O Stuermer
This study explored why lesioned retinal ganglion cell (RGC) axons regenerate successfully in the zebrafish optic nerve despite the presence of Rtn4b, the homologue of the rat neurite growth inhibitor RTN4-A/Nogo-A. Rat Nogo-A and zebrafish Rtn4b possess characteristic motifs (M1-4) in the Nogo-A-specific region, which contains delta20, the most inhibitory region of rat Nogo-A. To determine whether zebrafish M1-4 is inhibitory as rat M1-4 and Nogo-A delta20, proteins were recombinantly expressed and used as substrates for zebrafish single cell RGCs, mouse hippocampal neurons and goldfish, zebrafish and chick retinal explants...
May 30, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28524744/sphingosine-1-phosphate-signaling-in-bone-remodeling-multifaceted-roles-and-therapeutic-potential
#5
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...
June 7, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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-sphingosine-1-phosphate-receptor-2-in-bile-acid-induced-cholangiocyte-proliferation-and-cholestasis-induced-liver-injury-in-mice
#14
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 protein kinase B (AKT) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathways through sphingosine 1-phosphate receptor (S1PR) 2 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...
June 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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