ArticleMolecular neurobiology2015
The Role of TLR4 and Fyn Interaction on Lipopolysaccharide-Stimulated PAI-1 Expression in Astrocytes.
Article in Molecular neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence.Cell communication and signaling : CCS · 2024Review
- PAI-1 production by reactive astrocytes drives tissue dysfibrinolysis in multiple sclerosis models.Cellular and molecular life sciences : CMLS · 2022Article
- Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications.Mediators of inflammation · 2022Review
- Rosmarinic Acid Induces Proliferation Suppression of Hepatoma Cells Associated with NF-κB Signaling Pathway.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Rosmarinic acid inhibits cell proliferation, migration, and invasion and induces apoptosis in human glioma cells.International journal of molecular medicine · 2021Article
- Enteric Glia at the Crossroads between Intestinal Immune System and Epithelial Barrier: Implications for Parkinson Disease.International journal of molecular sciences · 2020Review
- tPA Deficiency Underlies Neurovascular Coupling Dysfunction by Amyloid-β.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Caffeoyl-Prolyl-Histidine Amide Inhibits Fyn and Alleviates Atopic Dermatitis-Like Phenotypes via Suppression of NF-κB Activation.International journal of molecular sciences · 2020Article
- Binding investigation and preliminary optimisation of the 3-amino-1,2,4-triazin-5(2H)-one core for the development of new Fyn inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Association of Lyn kinase with membrane rafts determines its negative influence on LPS-induced signaling.Molecular biology of the cell · 2017Article
- Regulatory region genetic variation is associated with FYN expression in Alzheimer's disease.Neurobiology of aging · 2017Article
- Posterior Reversible Encephalopathy Syndrome After Transplantation: a Review.Molecular neurobiology · 2016Review
- A possible role of microglia-derived nitric oxide by lipopolysaccharide in activation of astroglial pentose-phosphate pathway via the Keap1/Nrf2 system.Journal of neuroinflammation · 2016Article
- The Epigenetic Reader BRD2 as a Specific Modulator of PAI-1 Expression in Lipopolysaccharide-Stimulated Mouse Primary Astrocytes.Neurochemical research · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasminogen activator inhibitor-1 (PAI-1) is an endogenous inhibitor of tissue plasminogen activator (tPA) that acts as a neuromodulator in various neurophysiological and pathological conditions. Several researchers including us reported the induction of PAI-1 during inflammatory condition; however, the mechanism regulating PAI-1 induction is not yet clear. In this study, we investigated the role of non-receptor tyrosine kinase Fyn in the regulation of lipopolysaccharide (LPS)-induced upregulation of PAI-1 in rat primary astrocyte. The activation of toll-like receptor 4 (TLR4) signaling, induced by its ligand LPS, stimulated a physical interaction between TLR4 and Fyn along with phosphorylation of tyrosine residue in both molecules as determined by co-immunoprecipitation experiments. Immunofluorescence staining also showed increased co-localization of TLR4-Fyn on cultured rat primary astrocytes after LPS treatment. The increased TRLR4-Fyn interaction induced expression of PAI-1 through the activation of PI3k/Akt/NFĸB pathway. Treatment with Src kinase inhibitor (PP2) or transfection of Fyn small interfering RNA (siRNA) into cultured rat primary astrocytes inhibited phosphorylation of tyrosine residue of TLR4 and blocked the interaction between TLR4 and Fyn resulting to the inhibition of LPS-induced expression of PAI-1. The activation of PI3K/Akt/NFĸB signaling cascades was also inhibited by Fyn knockdown in rat primary astrocytes. The induction of PAI-1 in rat primary astrocytes, which resulted in downregulation of tPA activity in culture supernatants, inhibited neurite outgrowth in cultured rat primary cortical neuron. The inhibition of neurite extension was prevented by PP2 or Fyn siRNA treatment in rat primary astrocytes. These results suggest the critical physiological role of TRL4-Fyn interaction in the modulation of PAI-1-tPA axis in astrocytes during neuroinflammatory responses such as ischemia/reperfusion injuries.
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