ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Progranulin Controls Sepsis via C/EBPα-Regulated Il10 Transcription and Ubiquitin Ligase/Proteasome-Mediated Protein Degradation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Evaluation of serum progranulin as a biomarker for early detection of neonatal sepsis in a microbiological context.Scientific reports · 2026Article
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- Association among circulating erythropoietin-producing hepatoma A2, progranulin, and kidney function in individuals with diabetes.Journal of diabetes investigation · 2025Article
- Progranulin modulates inflammatory responses to immune challenges by suppressing circulating cytokine levels.Brain, behavior, & immunity - health · 2025Article
- Progranulin's Protective Mechanisms and Therapeutic Potential in Cardiovascular Disease.Cells · 2025Review
- Progranulin deficiency associates with postmenopausal osteoporosis via increasing ubiquitination of estrogen receptor α.Genes & diseases · 2025Article
- PGRN inhibits CD8Cancer immunology, immunotherapy : CII · 2024Article
- Analysis of the Genetic Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease through Biological Interaction Networks.International journal of molecular sciences · 2023Article
- Single-cell transcriptome profiling reveals heterogeneous neutrophils with prognostic values in sepsis.iScience · 2022Article
- TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity.The Journal of clinical investigation · 2021Article
- Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality.ESC heart failure · 2021Article
- Progranulin promotes diabetic fracture healing in mice with type 1 diabetes.Annals of the New York Academy of Sciences · 2020Article
- Progranulin Administration Attenuates β-Amyloid Deposition in the Hippocampus of 5xFAD Mice Through Modulating BACE1 Expression and Microglial Phagocytosis.Frontiers in cellular neuroscience · 2020Article
- Article
- Progranulin promotes melanoma progression by inhibiting natural killer cell recruitment to the tumor microenvironment.Cancer letters · 2019Article
- Anti-inflammatory Activity of MTL-CEBPA, a Small Activating RNA Drug, in LPS-Stimulated Monocytes and Humanized Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse Model.Frontiers in immunology · 2018Article
- Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Progranulin (PGRN) is a widely expressed, pleiotropic protein that is involved in diverse biological processes, including cellular proliferation, neuron development, and wound healing. However, the role of PGRN in the regulation of pathogen-induced systemic inflammation and the mechanisms involved have not been established. In this study, we show that PGRN-deficient mice display heightened mortality in models of polymicrobial sepsis and endotoxinemia, with increased tissue levels of inflammatory cytokines and reduced IL-10 production. Conversely, administration of rPGRN decreases the susceptibility of PGRN-deficient mice to LPS-induced endotoxemic shock and augments IL-10 production by LPS-activated macrophages in a TNFR-dependent manner. Molecular analysis reveals a direct role of the transcription factor C/EBPα in PGRN-regulated IL-10 expression. C/EBPα-deficient macrophages produce less IL-10 in response to LPS. Furthermore, mice deficient in C/EBPα in hematopoietic cells are highly vulnerable to LPS-induced septic shock. Lastly, the defective IL-10 production by PGRN-deficient cells is primarily due to reduced C/EBPα protein stability via the E3 ubiquitin-conjugating enzyme E6AP and proteasome-mediated degradation. To our knowledge, this study provides the first evidence that PGRN is a nonredundant regulator of systemic inflammation via modulating the levels and activity of C/EBPα, IL-10, and the ubiquitin-proteasome proteolysis pathway. The results bear strong and profound implications for PGRN insufficiency and its mutation-associated systemic and organ-specific inflammatory human diseases.
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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.