ArticleJournal of the American Society of Nephrology : JASN2012
Tissue plasminogen activator activates NF-κB through a pathway involving annexin A2/CD11b and integrin-linked kinase.
Article in Journal of the American Society of Nephrology : JASN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- A systematic review of the utility of biomarkers as aids in the early diagnosis and outcome prediction of bovine respiratory disease complex in feedlot cattle.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2022Pooled it
- The effects of Tissue-type Plasminogen Activator on PSC Activation.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Anti-Inflammatory and Antioxidant Activity ofPharmaceuticals (Basel, Switzerland) · 2025Article
- p90RSK modulates inter-and intracellular signaling in kidney diseases.Frontiers in cell and developmental biology · 2025Review
- Annexin A2: A Double-Edged Sword in Pathogen Infection.Pathogens (Basel, Switzerland) · 2024Review
- Minimal Change Disease: Pathogenetic Insights from Glomerular Proteomics.International journal of molecular sciences · 2024Article
- Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome.Nature communications · 2024Article
- Tissue-plasminogen activator effects on the phenotype of splenic myeloid cells in acute inflammation.Journal of inflammation (London, England) · 2024Article
- Recent Advances in Molecular and Cellular Functions of S100A10.Biomolecules · 2023Review
- Macrophage Function Modulated by tPA Signaling in Mouse Experimental Kidney Disease Models.International journal of molecular sciences · 2023Review
- Influenza A(H1N1)pdm09 Virus Aggravates Pathology of Blood Vessels in Wistar Rats with Premorbid Acute Cardiomyopathy.Viruses · 2023Article
- The intricate role of annexin A2 in kidney: a comprehensive review.Renal failure · 2023Review
- Single-cell transcriptome analysis of regenerating RGCs reveals potent glaucoma neural repair genes.Neuron · 2022Article
- Transcriptome of human neuroblastoma SH-SY5Y cells in response to 2B protein of enterovirus-A71.Scientific reports · 2022Article
- Roles of the tissue-type plasminogen activator in immune response.Cellular immunology · 2022Review
- Annexin A2 and Kidney Diseases.Frontiers in cell and developmental biology · 2022Review
- Integrin-Linked Kinase Expression Characterizes the Immunosuppressive Tumor Microenvironment in Colorectal Cancer and Regulates PD-L1 Expression and Immune Cell Cytotoxicity.Frontiers in oncology · 2022Article
- Insulin resistance is linked to a specific profile of immune activation in human subjects.Scientific reports · 2021Article
- Plasminogen Activators in Neurovascular and Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- Activation of the Adipose Tissue NLRP3 Inflammasome Pathway in Cancer Cachexia.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
NF-κB activation is central to the initiation and progression of inflammation, which contributes to the pathogenesis of CKD. Tissue plasminogen activator (tPA) modulates the NF-κB pathway, but the underlying mechanism remains unknown. We investigated the role of tPA signaling in macrophage NF-κB activation and found that tPA activated NF-κB in a time- and dose-dependent manner. tPA also induced the expression of the NF-κB-dependent chemokines IP-10 and MIP-1α. The protease-independent action of tPA required its membrane receptor, annexin A2. tPA induced the aggregation and interaction of annexin A2 with integrin CD11b, and ablation of CD11b or administration of anti-CD11b neutralizing antibody abolished the effect of tPA. Knockdown of the downstream effector of CD11b, integrin-linked kinase, or disruption of its engagement with CD11b also blocked tPA-induced NF-κB signaling. In vivo, tPA-knockout mice had reduced NF-κB signaling, fewer renal macrophages, and less collagen deposition than their counterparts. Taken together, these data suggest that tPA activates the NF-κB pathway in macrophages through a signaling pathway involving annexin A2/CD11b-mediated integrin-linked kinase.
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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 OpenQuestion graph.