ArticleThe Journal of biological chemistry2015
Tissue-type plasminogen activator (tPA) promotes M1 macrophage survival through p90 ribosomal S6 kinase (RSK) and p38 mitogen-activated protein kinase (MAPK) pathway.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Plat safeguards maternally aged oocytes against programmed cell death through activating the Erk1/2 pathway.Science China. Life sciences · 2026Article
- p90RSK modulates inter-and intracellular signaling in kidney diseases.Frontiers in cell and developmental biology · 2025Review
- Mechanisms of Macrophage Polarization Regulated by Oridonin: A Review.Journal of inflammation research · 2025Review
- HDL-cholesterol confers sensitivity of immunotherapy in nasopharyngeal carcinoma via remodeling tumor-associated macrophages towards the M1 phenotype.Journal for immunotherapy of cancer · 2024Article
- Tissue-plasminogen activator effects on the phenotype of splenic myeloid cells in acute inflammation.Journal of inflammation (London, England) · 2024Article
- A sub-10-nm, folic acid-conjugated gold nanoparticle as self-therapeutic treatment of tubulointerstitial fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Macrophage Function Modulated by tPA Signaling in Mouse Experimental Kidney Disease Models.International journal of molecular sciences · 2023Review
- CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells.Frontiers in cell and developmental biology · 2023Article
- Roles of the tissue-type plasminogen activator in immune response.Cellular immunology · 2022Review
- Plasminogen activator receptor assemblies in cell signaling, innate immunity, and inflammation.American journal of physiology. Cell physiology · 2021Review
- Review
- The Ser/Thr kinase p90RSK promotes kidney fibrosis by modulating fibroblast-epithelial crosstalk.The Journal of biological chemistry · 2019Article
- Role of p90RSK in Kidney and Other Diseases.International journal of molecular sciences · 2019Review
- Developing LRP1 Agonists into a Therapeutic Strategy in Acute Myocardial Infarction.International journal of molecular sciences · 2019Review
- Gene networks in basal cell carcinoma of the eyelid, analyzed using gene expression profiling.Oncology letters · 2018Article
- Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype.Nature communications · 2018Article
- Tissue-type plasminogen activator modulates macrophage M2 to M1 phenotypic change through annexin A2-mediated NF-κB pathway.Oncotarget · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophage accumulation is one of the hallmarks of progressive kidney disease. Resting macrophages have a finite lifespan, but become resistant to apoptosis in response to pathogenic cues, whereas the underlying mechanism remains unknown. Tissue-type plasminogen activator (tPA), a protease up-regulated in the kidneys with chronic injury, has been shown to promote macrophage accumulation and renal inflammation. We hypothesized that tPA may be the endogenous factor that promotes macrophage survival and extends their lifespan that leads to their accumulation in the injured kidneys. We examined the role of tPA in macrophage survival, and found that tPA protected macrophages from both staurosporine and H2O2-induced apoptosis. tPA promoted the survival of both resting and lipopolysaccharide- or interferon-γ-induced M1 macrophages, but failed to do so in the interleukin 4 (IL4)-induced M2 macrophages. In the kidneys with unilateral ureteral obstruction, there were significantly more apoptotic M1 macrophages in tPA-deficient mice than their wild-type counterparts, and obstruction-induced M1 macrophages accumulation and M1 chemokine expression were markedly reduced in these knock-out mice. The cytoprotective effect of tPA required its receptor, LDL receptor-related protein-1 (LRP-1). tPA induced the phosphorylation of Erk1/2, p90 ribosomal S6 kinase (RSK), and p38 in a temporal order. The tPA-mediated macrophage survival was eliminated by PD98059, BI-D1870, or sc68376, the specific inhibitors for Erk1/2, p90RSK, or p38, respectively. Thus, it is clear that tPA promoted M1 macrophage survival through its receptor LRP-1-mediated novel signaling cascade involving Erk1/2, p90RSK, and p38, which leads to the accumulation of these cells in the injured kidneys.
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