Dual effects of lysophosphatidic acid on human airway smooth muscle cell proliferation and survival

Ediger, Tracy L.; Toews, Myron L.

doi:10.1016/s1388-1981(01)00084-1

Cited by 13 publications

(12 citation statements)

References 21 publications

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“…LPA is a potent bioactive lipid that mediates several cellular responses such as proliferation, differentiation, suppression of apoptosis, tumor metastasis, and cytoskeletal reorganization (15,(21)(22)(23)(24)(25)(26)(27)(28). LPA mediates the broad range of cellular responses through the G-protein-coupled receptors LPA 1 /Edg-2, LPA 2 /Edg-4, and LPA 3 /Edg-7 (19).…”

Section: Discussionmentioning

confidence: 99%

“…In guinea pigs, administration of exogenous LPA into the airway enhances the response to acetylcholine (22) and infiltration of neutrophils (23). Other reports have shown that LPA induces airway smooth muscle contractility (24), proliferation (25), and transcription factor activation (26). In ovarian cancer cells, LPA induces both IL-6 and IL-8 expression (27,28).…”

mentioning

confidence: 98%

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Protein Kinase Cδ Mediates Lysophosphatidic Acid-induced NF-κB Activation and Interleukin-8 Secretion in Human Bronchial Epithelial Cells

Cummings

Zhao

Jacoby

et al. 2004

Journal of Biological Chemistry

121

174

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

Protein Kinase Cδ Mediates Lysophosphatidic Acid-induced NF-κB Activation and Interleukin-8 Secretion in Human Bronchial Epithelial Cells

Cummings

Zhao

Jacoby

et al. 2004

Journal of Biological Chemistry

121

174

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“…In hippocampal neurons, LPA also stimulates apoptosis and this response appears to be mediated via oxidative stress and increased NO production [Holtsberg et al, 1998]. Airway smooth muscle cells respond to low concentrations of LPA with mitogenesis, while higher concentrations of LPA stimulate apoptosis [Ediger and Toews, 2001]. S1P.…”

Section: Effects Of Lysophospholipids On Cell Survival and Apoptosismentioning

confidence: 99%

G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival

Radeff-Huang

Seasholtz

Matteo

et al. 2004

J of Cellular Biochemistry

176

178

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Agonist activation of a subset of G protein coupled receptors (GPCRs) stimulates cell proliferation, mimicking the better known effects of tyrosine kinase growth factors. Cell survival or apoptosis is also regulated via pathways initiated by stimulation of these same GPCRs. This review focuses on aspects of signaling by the lysophospholipid mediators, lysophosphatidic acid (LPA), and sphingosine 1 phosphate (S1P), which make these agonists uniquely capable of modulating cell growth and survival. The general features of GPCR coupling to specific G proteins, downstream effectors and signaling cascades are first reviewed. GPCR coupling to G(i) and Ras/MAPK or to G(q) and phospholipase generated second messengers are insufficient to regulate cell proliferation while G(12/13)/Rho engagement provides additional complementary signals required for cell proliferation. Survival is best predicted by coupling to G(i) pathways that regulate PI3K and Akt, but other signals generated through different G protein pathways are also implicated. The unique ability of LPA and S1P to concomitantly stimulate G(i), G(q), and G(12/13) pathways, given the proper complement of expressed LPA or S1P receptors, allows these receptors to support cell survival and proliferation. In pathophysiological situations, e.g., vascular disease, cancer, brain injury, and inflammation, components of the signaling cascade downstream of lysophospholipid receptors, in particular those involving Ras or Rho, may be altered. In addition, up or downregulation of LPA or S1P receptor subtypes, altering their ratio, and increased availability of the lysophospholipid ligands at sites of injury or inflammation, likely contribute to disease and may be important targets for therapeutic intervention.

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“…The majority of extracellular LPA is generated by hydrolysis of the choline moiety from lysophosphatidylcholine (LPC) by the enzyme autotaxin (ATX), which was recently shown to play an important role in a mouse model of allergic airway inflammation [5]. Relevant to the pathophysiology of asthma, LPA can enhance smooth muscle growth and contractility [6][7][8][9], induce mast cell activation [10][11][12][13], induce chemotaxis and migration of inflammatory cells [14][15][16][17], and elicit chemokine and cytokine release from bronchial epithelial cells [18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Novel Inhibitory Effect of a Lysophosphatidic Acid 2 Agonist on Allergen-Driven Airway Inflammation

Knowlden

Hillman

Chapman

et al. 2016

Am J Respir Cell Mol Biol

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Lysophosphatidic acid (LPA) is a pleiotropic lipid signaling molecule associated with asthma pathobiology. LPA elicits its effects by binding to at least six known cell surface G protein-coupled receptors (LPA1-6) that are expressed in the lung in a cell type-specific manner. LPA2 in particular has emerged as an attractive therapeutic target in asthma because it appears to transduce inhibitory or cell-protective signals. We studied a novel and specific small molecule LPA2 agonist (2-[4-(1,3-dioxo-1H,3H-benzoisoquinolin-2-yl)butylsulfamoyl] benzoic acid [DBIBB]) in a mouse model of house dust mite-induced allergic airway inflammation. Mice injected with DBIBB developed significantly less airway and lung inflammation compared with vehicle-treated controls. Levels of lung Th2 cytokines were also significantly attenuated by DBIBB. We conclude that pharmacologic activation of LPA2 attenuates Th2-driven allergic airway inflammation in a mouse model of asthma. Targeting LPA receptor signaling holds therapeutic promise in allergic asthma.

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Dual effects of lysophosphatidic acid on human airway smooth muscle cell proliferation and survival

Cited by 13 publications

References 21 publications

Protein Kinase Cδ Mediates Lysophosphatidic Acid-induced NF-κB Activation and Interleukin-8 Secretion in Human Bronchial Epithelial Cells

Protein Kinase Cδ Mediates Lysophosphatidic Acid-induced NF-κB Activation and Interleukin-8 Secretion in Human Bronchial Epithelial Cells

G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival

Novel Inhibitory Effect of a Lysophosphatidic Acid 2 Agonist on Allergen-Driven Airway Inflammation

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