ArticleThe American journal of pathology2014
Myeloid-derived tissue-type plasminogen activator promotes macrophage motility through FAK, Rac1, and NF-κB pathways.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Polydopamine-Coated Surfaces Promote Adhesion, Migration, Proliferation, Chemoresistance, Stemness, and Epithelial-Mesenchymal Transition of Human Prostate Cancer Cell Lines In Vitro via Integrin αInternational journal of molecular sciences · 2026Article
- Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19.Research and practice in thrombosis and haemostasis · 2023Article
- Macrophage Function Modulated by tPA Signaling in Mouse Experimental Kidney Disease Models.International journal of molecular sciences · 2023Review
- Netrin-1 controls inflammation in response to ischemic stroke through altering microglia phenotype.Frontiers in immunology · 2023Article
- Activation of the NLRP3 inflammasome by RAC1 mediates a new mechanism in diabetic nephropathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Review
- The Ser/Thr kinase p90RSK promotes kidney fibrosis by modulating fibroblast-epithelial crosstalk.The Journal of biological chemistry · 2019Article
- Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in Dialysis-Dependent AKI Patients.Kidney international reports · 2018Article
- Tissue-type plasminogen activator modulates macrophage M2 to M1 phenotypic change through annexin A2-mediated NF-κB pathway.Oncotarget · 2017Article
- Tissue-type plasminogen activator (tPA) promotes M1 macrophage survival through p90 ribosomal S6 kinase (RSK) and p38 mitogen-activated protein kinase (MAPK) pathway.The Journal of biological chemistry · 2015Article
- LRP-1: functions, signaling and implications in kidney and other diseases.International journal of molecular sciences · 2014Review
- TRPM2 mediates ischemic kidney injury and oxidant stress through RAC1.The Journal of clinical investigation · 2014Article
- Tissue Plasminogen Activator: Side Effects and Signaling.Journal of drug design and research · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Macrophage accumulation is one of the hallmarks of progressive kidney disease. Tissue-type plasminogen activator (tPA) is known to promote macrophage infiltration and renal inflammation during chronic kidney injury. However, the underlying mechanism remains largely unknown. We examined the role of tPA in macrophage motility in vivo by tracking fluorescence-labeled bone marrow-derived macrophages, and found that tPA-deficient mice had markedly fewer infiltrating fluorescence-labeled macrophages than the wild-type (WT) mice. Experiments in bone marrow chimeric mice further demonstrated that myeloid cells are the main source of endogenous tPA that promotes macrophage migration. In vitro studies showed that tPA promoted macrophage motility through its CD11b-mediated protease-independent function; and focal adhesion kinase (FAK), Rac-1, and NF-κB were indispensable to tPA-induced macrophage migration as either infection of FAK dominant-negative adenovirus or treatment with a Rac-1-specific inhibitor or NF-κB inhibitor abolished the effect of tPA. Moreover, ectopic FAK mimicked tPA and induced macrophage motility. tPA also activated migratory signaling in vivo. The accumulation of phospho-FAK-positive CD11b macrophages in the obstructed kidneys from WT mice was clearly attenuated in tPA knockout mice, which also displayed lower Rac-1 activity than their WT counterparts. Therefore, our results indicate that myeloid-derived tPA promotes macrophage migration through a novel signaling cascade involving FAK, Rac-1, and NF-κB.
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