ArticleCell death & disease2022
EGFR tyrosine kinase activity and Rab GTPases coordinate EGFR trafficking to regulate macrophage activation in sepsis.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- EGFR orchestrates neutrophil activation and NETosis via CEBPβ-dependent PGLYRP1 induction.Cell death and differentiation · 2026Article
- Exosomal microRNA-448 suppresses the malignant behaviors of liver cancer cells by targeting RAB7A and inhibiting glycolysis.Oncology letters · 2026Article
- M1 Macrophage-Derived Small Extracellular Vesicles as Synergistic Nanotherapeutics: Harnessing Intrinsic Anticancer Activity and Drug Delivery Capacity.Journal of extracellular vesicles · 2026Article
- Interaction networks of macrophage glycolysis and inflammation in sepsis: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Metabolic reprogramming, macrophage polarization, and intercellular crosstalk in pelvic inflammatory disease: emerging paradigms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Cytoskeletal remodeling via CAMSAP3 downregulation drives resistance to osimertinib in NSCLC cells.Cell death & disease · 2025Article
- TMPRSS11E-mediated TFR1 cleavage influences IFN-γR2 internalization and the macrophage innate response.Communications biology · 2025Article
- Effect of acupuncture on brain microenvironment in rats with post-stroke limb spasticity based on single-cell transcriptome sequencing technology.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- A scalable proteogenomic framework for dissecting phospho-signaling pathways in primary immune cells.bioRxiv : the preprint server for biology · 2025Article
- Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarction.Materials today. Bio · 2025Article
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- An "inside-out"-guided genetically engineered hydrogel for augmenting aged bone regeneration.Bioactive materials · 2025Article
- HIF-1α: a bridge connecting sepsis and acute respiratory distress syndrome.European journal of medical research · 2025Review
- Article
- Fibroblast EGFR signaling mediates ricin toxin-induced acute lung injury via EGR1/CXCL1 axis.Archives of toxicology · 2025Article
- NSC-derived extracellular vesicles-mediates neuronal plasticity enhancement in vascular dementia via transferring miR-210.Acta neuropathologica communications · 2025Article
- Programmed Cell Death Protein 10 (PDCD10) Regulates Vesicle Trafficking and Contributes to the Progression of Clear Cell Renal Cell Carcinoma.Journal of extracellular vesicles · 2025Article
- GALNT3 in Ischemia-Reperfusion Injury of the Kidney.Journal of the American Society of Nephrology : JASN · 2025Article
- The Anti-Inflammatory Effects of Formononetin, an Active Constituent ofMolecules (Basel, Switzerland) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EGFR phosphorylation is required for TLR4-mediated macrophage activation during sepsis. However, whether and how intracellular EGFR is transported during endotoxemia have largely been unknown. Here, we show that LPS promotes high levels cell surface expression of EGFR in macrophages through two different transport mechanisms. On one hand, Rab10 is required for EEA1-mediated the membrane translocation of EGFR from the Golgi. On the other hand, EGFR phosphorylation prevents its endocytosis in a kinase activity-dependent manner. Erlotinib, an EGFR tyrosine kinase inhibitor, significantly reduced membrane EGFR expression in LPS-activated macrophage. Mechanistically, upon LPS induced TLR4/EGFR phosphorylation, MAPK14 phosphorylated Rab7a at S72 impaired membrane receptor late endocytosis, which maintains EGFR membrane localization though blocking its lysosomal degradation. Meanwhile, Rab5a is also involved in the early endocytosis of EGFR. Subsequently, inhibition of EGFR phosphorylation switches M1 phenotype to M2 phenotype and alleviates sepsis-induced acute lung injury. Mechanistic study demonstrated that Erlotinib suppressed glycolysis-dependent M1 polarization via PKM2/HIF-1ɑ pathway and promoted M2 polarization through up-regulating PPARγ induced glutamine metabolism. Collectively, our data elucidated a more in-depth mechanism of macrophages activation, and provided stronger evidence supporting EGFR as a potential therapeutic target for the treatment of sepsis.
Indexed as
Identifiers
What OpenQuestion holds
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.