ArticleJournal of neuroinflammation2017
Lysophosphatidic acid via LPA-receptor 5/protein kinase D-dependent pathways induces a motile and pro-inflammatory microglial phenotype.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Context-dependent lysophosphatidic acid signalling in inflammation: evidence hierarchy, myeloid regulation and translational gaps.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Differential downstream signaling in microglia lacking Alzheimer's-related TREM2 or its adaptor TYROBP/DAP12.Molecular neurodegeneration advances · 2026Article
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Unraveling the Role of Autotaxin and Lysophosphatidic Acid in Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Potential.International journal of molecular sciences · 2025Review
- LPAR6 Participates in Neuropathic Pain by Mediating Astrocyte Cells via ROCK2/NF-κB Signal Pathway.Molecular neurobiology · 2024Article
- Design Principle of Heparanase Inhibitors: A Combined In Vitro and In Silico Study.ACS medicinal chemistry letters · 2024Article
- Lysophospholipid receptors in neurodegeneration and neuroprotection.Exploration of neuroprotective therapy · 2024Article
- Lysophosphatidic acid exerts protective effects on HEI-OC1 cells against cytotoxicity of cisplatin by decreasing apoptosis, excessive autophagy, and accumulation of ROS.Cell death discovery · 2023Article
- Poly(ADP-ribose) polymerase family member 14 promotes functional recovery after spinal cord injury through regulating microglia M1/M2 polarization via STAT1/6 pathway.Neural regeneration research · 2023Article
- Shear-induced phenotypic transformation of microglia in vitro.Biophysical journal · 2023Article
- Emerging roles of lysophosphatidic acid receptor subtype 5 (LPAR5) in inflammatory diseases and cancer.Pharmacology & therapeutics · 2023Review
- Sodium-glucose cotransporter 2 inhibitor ameliorates high fat diet-induced hypothalamic-pituitary-ovarian axis disorders.The Journal of physiology · 2022Review
- Microglia-mediated neuroinflammation and neuroplasticity after stroke.Frontiers in cellular neuroscience · 2022Review
- PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery.Autophagy · 2021Article
- Disrupted Blood-Brain Barrier and Mitochondrial Impairment by Autotaxin-Lysophosphatidic Acid Axis in Postischemic Stroke.Journal of the American Heart Association · 2021Article
- Critical Roles of Lysophospholipid Receptors in Activation of Neuroglia and Their Neuroinflammatory Responses.International journal of molecular sciences · 2021Review
- Review
- Opposing functions of β-arrestin 1 and 2 in Parkinson's disease via microglia inflammation and Nprl3.Cell death and differentiation · 2021Article
- LPAR5 promotes thyroid carcinoma cell proliferation and migration by activating class IA PI3K catalytic subunit p110β.Cancer science · 2021Article
- Lysophosphatidic Acid Signalling in Nervous System Development and Function.Neuromolecular medicine · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundExtracellular lysophosphatidic acid (LPA) species transmit signals via six different G protein-coupled receptors (LPAR1-6) and are indispensible for brain development and function of the nervous system. However, under neuroinflammatory conditions or brain damage, LPA levels increase, thereby inducing signaling cascades that counteract brain function. We describe a critical role for 1-oleyl-2-hydroxy-sn-glycero-3-phosphate (termed "LPA" throughout our study) in mediating a motile and pro-inflammatory microglial phenotype via LPAR5 that couples to protein kinase D (PKD)-mediated pathways.
methodsUsing the xCELLigence system and time-lapse microscopy, we investigated the migrational response of microglial cells. Different M1 and M2 markers were analyzed by confocal microscopy, flow cytometry, and immunoblotting. Using qPCR and ELISA, we studied the expression of migratory genes and quantitated the secretion of pro-inflammatory cytokines and chemokines, respectively. Different transcription factors that promote the regulation of pro-inflammatory genes were analyzed by western blot. Reactive oxygen species (ROS) and nitric oxide (NO) production, phagocytosis, and microglial cytotoxicity were determined using commercially available assay kits.
resultsLPA induces MAPK family and AKT activation and pro-inflammatory transcription factors' phosphorylation (NF-κB, c-Jun, STAT1, and STAT3) that were inhibited by both LPAR5 and PKD family antagonists. LPA increases migratory capacity, induces secretion of pro-inflammatory cytokines and chemokines and expression of M1 markers, enhances production of ROS and NO by microglia, and augments cytotoxicity of microglial cell-conditioned medium towards neurons. The PKD family inhibitor blunted all of these effects. We propose that interference with this signaling axis could aid in the development of new therapeutic approaches to control neuroinflammation under conditions of overshooting LPA production.
conclusionsIn the present study, we show that inflammatory LPA levels increased the migratory response of microglia and promoted a pro-inflammatory phenotype via the LPAR5/PKD axis. Interference with this signaling axis reduced microglial migration, blunted microglial cytotoxicity, and abrogated the expression and secretion of pro-inflammatory mediators.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.