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Lysophosphatidic acid

Feng Hao, Fuqiang Zhang, Daniel Dongwei Wu, Dong An, Jing Shi, Guohong Li, Xuemin Xu, Mei-Zhen Cui
Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation...
October 19, 2016: American Journal of Physiology. Cell Physiology
Aihua Xu, Md Ahsanul Kabir Khan, Fangzhi Chen, Zhaohui Zhong, Han-Chun Chen, Yuanda Song
Autotaxin (ATX) as an important tumor cell motility-stimulating factor is upregulated in many different types of cancer. ATX, a member of the ectonucleotide pyrophosphatase and phosphodiesterase family of enzymes, possesses lysophospholipase D activity which hydrolyzes lysophosphatidylcholine to generate the potent tumor growth factor and mitogen lysophosphatidic acid (LPA). LPA acts on specific G-protein-coupled receptors, thereby regulating cell growth, migration, and survival. This study aimed to investigate the differences in gene expression pattern of ATX between cancerous and adjacent normal tissue of human renal cell carcinoma (RCC) and bladder carcinoma (BC) and find the correlation between ATX expression and clinicopathological features of both of these carcinomas...
November 2016: Medical Oncology
Gretchen Bain, Kristen E Shannon, Fei Huang, Janice Darlington, Lance Goulet, Patricia Prodanovich, Gina L Ma, Angelina M Santini, Adam J Stein, Dave Lonergan, Christopher D King, Imelda Calderon, Andiliy Lai, John H Hutchinson, Jilly F Evans
Autotaxin (ATX) is a secreted glycoprotein that converts lysophosphatidylcholine (LPC) to the bioactive phospholipid lysophosphatidic acid (LPA) and is the major enzyme generating circulating LPA. Inhibition of LPA signaling has profound anti-fibrotic effects in multiple organ systems including the lung, kidney, skin and peritoneum. However, other LPA-generating pathways exist and the role of ATX in localized tissue LPA production and fibrosis remains unclear and controversial. In this study, we describe the preclinical pharmacological, pharmacokinetic and pharmacodynamic properties of a novel small-molecule ATX inhibitor [3-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl) thio)-2-fluorobenzoic acid sodium salt] (PAT-505)...
October 17, 2016: Journal of Pharmacology and Experimental Therapeutics
Caojian Zuo
OBJECTIVE: Cardiac fibroblasts play a vital role in the progression of fibrotic cardiac remodeling in hypertensive and failing heart. Osteoglycin (OGN) is implicated as a key regulator of left ventricular mass. However, its precise molecular role in cardiac fibrosis remains unknown. This study aims to investigate the impact of OGN in hypertensive cardiac remodeling. DESIGN AND METHOD: OGN deficient mice and its wildtype (WT) littermates were subjected to either angiotensin II (Ang II) infusion or pressure overload induced by transverse aortic constriction (TAC)...
September 2016: Journal of Hypertension
Sung-Hee Hwang, Byung-Hwan Lee, Sun-Hye Choi, Hyeon-Joong Kim, Kyung Jong Won, Hwan Myung Lee, Hyewon Rhim, Hyoung-Chun Kim, Seung-Yeol Nah
BACKGROUND: Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are used as an in vitro model for screening therapeutic agents that promote angiogenesis and wound healing. We recently isolated gintonin, a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand, from ginseng...
October 2016: Journal of Ginseng Research
Cody Kime, Masayo Sakaki-Yumoto, Leeanne Goodrich, Yohei Hayashi, Salma Sami, Rik Derynck, Michio Asahi, Barbara Panning, Shinya Yamanaka, Kiichiro Tomoda
Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion...
October 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
Z Touat-Hamici, H Weidmann, Y Blum, C Proust, H Durand, F Iannacci, V Codoni, P Gaignard, P Thérond, M Civelek, A S Karabina, A J Lusis, F Cambien, E Ninio
AIMS: Lipid phosphate phosphatase 3 (LPP3; PPAP2B) is a transmembrane protein dephosphorylating and thereby terminating signalling of lipid substrates including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Human LPP3 possesses a cell adhesion motif that allows interaction with integrins. A polymorphism (rs17114036) in PPAP2B is associated with coronary artery disease, which prompted us to investigate the possible role of LPP3 in human endothelial dysfunction, a condition promoting atherosclerosis...
September 30, 2016: Cardiovascular Research
Ru Li, Cordula Klockenbusch, Liwen Lin, Honghui Jiang, Shujun Lin, Juergen Kast
Physiological stimuli such as thrombin, or pathological stimuli such as lysophosphatidic acid (LPA), activate platelets. The activated platelets bind to monocytes through P-selectin-PSGL-1 interactions, but also release the contents of their granules, commonly called "platelet releasate". It is known that monocytes in contact with platelet releasate produce reactive oxygen species (ROS). Reversible cysteine oxidation by ROS is considered to be a potential regulator of protein function. In a previous study, we used THP-1 monocytic cells exposed to LPA- or thrombin-induced platelet releasate and a modified biotin switch assay to unravel the biological processes that are influenced by reversible cysteine oxidation...
October 3, 2016: Journal of Proteome Research
Ni Xu, Ming-Zheng Wu, Xue-Ting Deng, Ping-Chuan Ma, Ze-Hua Li, Lei Liang, Meng-Fan Xia, Dong Cui, Duan-Duan He, Yuan Zong, Zhong Xie, Xue-Jun Song
UNLABELLED: Neuropathic pain, often caused by nerve injury, is a major clinical challenge. Mechanisms that underlie neuropathic pain remain elusive and effective medications are limited. Numerous investigations of pain mechanisms have focused on alterations and phenotypic switches of the nociceptive transmitters and modulators, as well as on their receptors and downstream signaling pathways that have already exerted roles in the pain processes of mature nervous systems. We have demonstrated recently that nerve injury may elicit neuronal alterations that recapitulate events occurring during development...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ryoko Tsukahara, Hiroshi Ueda
Lysophosphatidic acid (LPA) initiates demyelination following peripheral nerve injury, which causes neuropathic pain. Our previous in vivo and ex vivo studies using mice have demonstrated that LPA-induced demyelination of spinal dorsal roots is attributed by the LPA1-type receptor-mediated down-regulation of myelin-related molecules, such as MBP and MPZ. In this study using S16 mature-type Schwann cells, we found that LPA-induced down-regulation of myelin-related genes is attributed by the activation of LPA1 receptor, Rho kinase, and p300, leading to an acetylation of NFκB, which down-regulates the transcription of Sox10, MBP and MPZ genes...
September 12, 2016: Journal of Pharmacological Sciences
Irit Miller, Dana Chuderland, Hadas Grossman, Raphael Ron-El, Ido Ben-Ami, Ruth Shalgi
CONTEXT: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of assisted reproductive technologies (ART).This complex syndrome is known to involve massive angiogenesis and inflammation. We have previously established the anti-angiogenic involvement of pigment epithelium-derived factor (PEDF) in the pathophysiology and treatment of OHSS. OBJECTIVE: Evaluate the anti-inflammatory role of PEDF in OHSS. DESIGN: In-vivo mouse OHSS-model and in-vitro cultures of granulosa cells...
September 28, 2016: Journal of Clinical Endocrinology and Metabolism
Natalie A Wheeler, Babette Fuss, Pamela E Knapp, ShiPing Zou
White matter injury has been frequently reported in HIV(+) patients. Previous studies showed that HIV-1 Tat (transactivator of transcription), a viral protein that is produced and secreted by HIV-infected cells, is toxic to young, immature oligodendrocytes (OLGs). Adding Tat to the culture medium reduced the viability of immature OLGs, and the surviving OLGs exhibited reduced process networks. OLGs produce and secrete autotaxin (ATX), an ecto-enzyme containing a lysophospholipase D (lysoPLD) activity that converts lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a lipid signaling molecule that stimulates OLG differentiation...
October 2016: ASN Neuro
J J McDougall, S Albacete, N Schuelert, P G Mitchell, C Lin, J L Oskins, H H Bui, M G Chambers
OBJECTIVE: Emerging evidence suggests that osteoarthritis (OA) has a neuropathic component; however, the identity of the molecules responsible for this peripheral neuropathy is unknown. The aim of this study was to determine the contribution of the bioactive lipid lysophosphatidic acid (LPA) to joint neuropathy and pain. DESIGN: Male Lewis rats received an intra-articular injection of 50 μg of LPA into the knee and allowed to recover for up to 21 days. Saphenous nerve myelination was assessed by g-ratio calculation from electron micrographs and afferent nerve damage visualised by activation transcription factor-3 (ATF-3) expression...
September 17, 2016: Osteoarthritis and Cartilage
Ivanka Dacheva, Christoph Ullmer, Karolina Ceglowska, Everson Nogoceke, Guido Hartmann, Stephan Müller, Robert Rejdak, Katarzyna Nowomiejska, Michael Reich, Matthias Nobl, Tamer Tandogan, Florian T A Kretz, Gerd U Auffarth, Michael J Koss
PURPOSE: To analyze the levels of lysophosphatidic acids (LPAs) and autotaxin (ATX) in undiluted vitreous of untreated patients with retinal vein occlusion (RVO). METHODS: Sixty-four vitreous samples (40 RVO, 24 controls with idiopathic floaters) were analyzed in this retrospective case series using LC/MS for LPAs 16:0, 18:0, 18:1, 20:4, and ELISA kits or Luminex technology for ATX, angiopoetin-1 (ANG-1), interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), pigment epithelium-derived factor (PEDF), and vascular endothelial growth factor (VEGF)...
July 12, 2016: Retina
E Sinderewicz, K Grycmacher, D Boruszewska, I Kowalczyk-Zięba, I Woclawek-Potocka
Lysophosphatidic acid (LPA) exerts various actions on the mammalian reproductive system. In cows, LPA stimulates the synthesis and secretion of luteotropic factors in the ovary, which affects the growth and development of ovarian follicles. The role of LPA in granulosa cells, oocyte and oocyte-cumulus complex (COC) has previously been investigated; but its role in the theca layer, which is an important structural and functional component of the ovarian follicle, is still unclear. The goal of this study was to investigate the expression of LPA in theca cells originating from different bovine ovarian follicle types...
September 20, 2016: Reproduction in Domestic Animals, Zuchthygiene
Caojian Zuo
OBJECTIVE: Cardiac fibroblasts play a vital role in the progression of fibrotic cardiac remodeling in hypertensive and failing heart. Osteoglycin (OGN) is implicated as a key regulator of left ventricular mass. However, its precise molecular role in cardiac fibrosis remains unknown. This study aims to investigate the impact of OGN in hypertensive cardiac remodeling. DESIGN AND METHOD: OGN deficient mice and its wildtype (WT) littermates were subjected to either angiotensin II (Ang II) infusion or pressure overload induced by transverse aortic constriction (TAC)...
September 2016: Journal of Hypertension
Jin Cheng, Sadhna Sahani, Torben Johann Hausrat, Jenq-Wei Yang, Haichao Ji, Nikolai Schmarowski, Heiko Endle, Xinfeng Liu, Yunbo Li, Rahel Böttche, Konstantin Radyushkin, Hans M Maric, Anna Hoerder-Suabedissen, Zoltán Molnár, Pierre-Hugues Prouvot, Thorsten Trimbuch, Olaf Ninnemann, Jisen Huai, Wei Fan, Barbara Visentin, Roger Sabbadini, Kristian Strømgaard, Albrecht Stroh, Heiko J Luhmann, Matthias Kneussel, Robert Nitsch, Johannes Vogt
Precise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information. Here, we show that PRG-2, a phospholipid-interacting molecule, is important for thalamocortical axon guidance. Developing thalamocortical fibers both in PRG-2 full knockout (KO) and in thalamus-specific KO mice prematurely entered the cortical plate, eventually innervating non-corresponding barrels. This misrouting relied on lost axonal sensitivity toward lysophosphatidic acid (LPA), which failed to repel PRG-2-deficient thalamocortical fibers...
October 5, 2016: Neuron
Masahiko Kanehira, Tohru Fujiwara, Shinji Nakajima, Yoko Okitsu, Yasushi Onishi, Noriko Fukuhara, Ryo Ichinohasama, Yoshinori Okada, Hideo Harigae
Mesenchymal stromal cells (MSCs) are multipotent progenitor cells and there is much interest in how MSCs contribute to the regulation of the tumor microenvironment. Whether MSCs exert a supportive or suppressive effect on tumor progression is still controversial, but is likely dependent on a variety of factors that are tumor-type dependent. Multiple myeloma (MM) is characterized by growth of malignant plasma cells in the bone marrow. It has been shown that the progression of MM is governed by MSCs, which act as a stroma of the myeloma cells...
September 19, 2016: Stem Cells
K Thirunavukkarasu, C A Swearingen, J L Oskins, C Lin, H H Bui, S B Jones, L A Pfeifer, B H Norman, P G Mitchell, M G Chambers
OBJECTIVE: Autotaxin is a secreted lysophospholipase that mediates the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA), a bioactive lipid mediator. Autotaxin levels in plasma and synovial fluid correlate with disease severity in patients with knee osteoarthritis (OA). The goal of this study was to develop and characterize a novel small molecule inhibitor of autotaxin to inhibit LPA production in vivo and determine its efficacy in animal models of musculoskeletal pain...
September 13, 2016: Osteoarthritis and Cartilage
Koryun Mirzoyan, Anna Baïotto, Aude Dupuy, Dimitri Marsal, Colette Denis, Claire Vinel, Pierre Sicard, Justine Bertrand-Michel, Jean-Loup Bascands, Joost P Schanstra, Julie Klein, Jean-Sébastien Saulnier-Blache
Increased incidence of chronic kidney disease (CKD) with consecutive progression to end-stage renal disease represents a significant burden to healthcare systems. Renal tubulointerstitial fibrosis (TIF) is a classical hallmark of CKD and is well correlated with the loss of renal function. The bioactive lysophospholipid lysophosphatidic acid (LPA), acting through specific G-protein-coupled receptors, was previously shown to be involved in TIF development in a mouse model of unilateral ureteral obstruction. Here, we study the role of LPA in a mouse subjected to subtotal nephrectomy (SNx), a more chronic and progressive model of CKD...
September 17, 2016: Journal of Physiology and Biochemistry
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