ArticleJournal of neuroinflammation2012
Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 101 citations in OpenAlex.
- Allergy-specific Phenome-Wide Association Study for Immunogenes in Turkish Children.Scientific reports · 2016Trial
- Stress-induced plasminogen activator inhibitor-1 (PAI-1) as a blood biomarker and brain risk factor for PTSD.Molecular psychiatry · 2026Article
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- Comprehensive Proteomic Profiling Reveals Dysregulation of Angiogenesis and Inflammatory Pathways in the Brains of SIRT3 Knockout Mice.Brain sciences · 2026Article
- Plasma Plasminogen Activator Inhibitor-1 as a Biomarker for Disease Activity and Pharmaco-Response Prediction in Pediatric Epilepsy: A Prospective Cohort Study.Neuropsychiatric disease and treatment · 2026Article
- SARS-CoV-2 infection in hiPSC-derived neurons is cathepsin-dependent and causes differential accumulation of HIF1ɑ and phosphorylated tau.Molecular therapy. Nucleic acids · 2025Article
- Microglia-astrocyte crosstalk following ischemic stroke.Molecular brain · 2025Review
- Anti-TNFα and Anti-IL-1β Monoclonal Antibodies Preserve BV-2 Microglial Homeostasis Under Hypoxia by Mitigating Inflammatory Reactivity and ATF4/MAPK-Mediated Apoptosis.Antioxidants (Basel, Switzerland) · 2025Article
- Construction of an lncRNA-mediated ceRNA network to investigate the inflammatory regulatory mechanisms of ischemic stroke.PloS one · 2025Article
- Microglial Melatonin Receptor 1 Degrades Pathological Alpha-Synuclein Through Activating LC3-Associated Phagocytosis In Vitro.CNS neuroscience & therapeutics · 2024Article
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- Microglia in physiological conditions and the importance of understanding their homeostatic functions in the arcuate nucleus.Frontiers in immunology · 2024Review
- Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand 1.Frontiers in immunology · 2024Article
- Article
- Phenomic Microglia Diversity as a Druggable Target in the Hippocampus in Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- The role of monocytes in optic nerve injury.Neural regeneration research · 2023Review
- Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system.Communications biology · 2023Article
- Emerging Role of MicroRNA-30c in Neurological Disorders.International journal of molecular sciences · 2022Review
- Impact of Aβ40 and Aβ42 Fibrils on the Transcriptome of Primary Astrocytes and Microglia.Biomedicines · 2022Article
- Dysregulation of neuroprotective astrocytes, a spectrum of microglial activation states, and altered hippocampal neurogenesis are revealed by single-cell RNA sequencing in prion disease.Acta neuropathologica communications · 2022Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPlasminogen activator inhibitor type 1 (PAI-1) is the primary inhibitor of urokinase type plasminogen activators (uPA) and tissue type plasminogen activators (tPA), which mediate fibrinolysis. PAI-1 is also involved in the innate immunity by regulating cell migration and phagocytosis. However, little is known about the role of PAI-1 in the central nervous system.
methodsIn this study, we identified PAI-1 in the culture medium of mouse mixed glial cells by liquid chromatography and tandem mass spectrometry. Secretion of PAI-1 from glial cultures was detected by ELISA and western blotting analysis. Cell migration was evaluated by in vitro scratch-wound healing assay or Boyden chamber assay and an in vivo stab wound injury model. Phagocytic activity was measured by uptake of zymosan particles.
resultsThe levels of PAI-1 mRNA and protein expression were increased by lipopolysaccharide and interferon-γ stimulation in both microglia and astrocytes. PAI-1 promoted the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein (LRP) 1/Janus kinase (JAK)/signal transducer and activator of transcription (STAT)1 axis. PAI-1 also increased microglial migration in vivo when injected into mouse brain. PAI-1-mediated microglial migration was independent of protease inhibition, because an R346A mutant of PAI-1 with impaired PA inhibitory activity also promoted microglial migration. Moreover, PAI-1 was able to modulate microglial phagocytic activity. PAI-1 inhibited microglial engulfment of zymosan particles in a vitronectin- and Toll-like receptor 2/6-dependent manner.
conclusionOur results indicate that glia-derived PAI-1 may regulate microglial migration and phagocytosis in an autocrine or paracrine manner. This may have important implications in the regulation of brain microglial activities in health and disease.
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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 OpenQuestion graph.