ArticleJCI insight2021
Endothelial SOCS3 maintains homeostasis and promotes survival in endotoxemic mice.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Insights from integrative spatial transcriptomics in sepsis-associated acute kidney injury.Nature reviews. Nephrology · 2026Review
- The anti-interleukin-6 antibody ALD518-P18 mitigates murine kidney ischemia-reperfusion injury.Scientific reports · 2026Article
- Brain endothelial PTPRO drives LPS-induced metabolic reprogramming and neuroinflammation in sepsis-associated encephalopathy.Journal of neuroinflammation · 2026Article
- RIPK3 Protects Against Endothelial Activation and Vascular Permeability in a Mouse Model of Ischemia-Reperfusion Injury.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Endothelial cells retain inflammatory memory through chromatin remodeling in a two-hit model of infection-induced inflammation.American journal of physiology. Cell physiology · 2025Article
- Endothelial Cell Stimulator of Interferon Genes Regulates IL-6 Production and Is Required for Pathologic Cardiac Hypertrophy and Contractile Dysfunction in Experimental Heart Failure.The American journal of pathology · 2025Article
- The intersection of influenza infection and autoimmunity.Frontiers in immunology · 2025Review
- GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3.Experimental and therapeutic medicine · 2024Article
- A transient brain endothelial translatome response to endotoxin is associated with mild cognitive changes post-shock in young mice.Neuroscience · 2024Article
- Mesenchymal stem cell-derived extracellular vesicles targeting irradiated intestine exert therapeutic effects.Theranostics · 2024Article
- MARCH family E3 ubiquitin ligases selectively target and degrade cadherin family proteins.PloS one · 2024Article
- Modulation of recovery from neonatal hyperoxic lung injury by sex as a biological variable.Redox biology · 2023Article
- An in vitro model of the macrophage-endothelial interface to characterize CAR T-cell induced cytokine storm.Scientific reports · 2023Article
- Shock drives a STAT3 and JunB-mediated coordinated transcriptional and DNA methylation response in the endothelium.Journal of cell science · 2023Article
- Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data.International journal of molecular sciences · 2023Article
- 4-Octyl itaconate attenuates LPS-induced acute kidney injury by activating Nrf2 and inhibiting STAT3 signaling.Molecular medicine (Cambridge, Mass.) · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Remarkable sex-specific differences at single-cell resolution in neonatal hyperoxic lung injury.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- SOCS3 limits TNF and endotoxin-induced endothelial dysfunction by blocking a required autocrine interleukin-6 signal in human endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Classical Signaling and Trans-Signaling Pathways Stimulated byInternational journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
SOCS3 is the main inhibitor of the JAK/STAT3 pathway. This pathway is activated by interleukin 6 (IL-6), a major mediator of the cytokine storm during shock. To determine its role in the vascular response to shock, we challenged mice lacking SOCS3 in the adult endothelium (SOCS3iEKO) with a nonlethal dose of lipopolysaccharide (LPS). SOCS3iEKO mice died 16-24 hours postinjection after severe kidney failure. Loss of SOCS3 led to an LPS-induced type I IFN-like program and high expression of prothrombotic and proadhesive genes. Consistently, we observed intraluminal leukocyte adhesion and neutrophil extracellular trap-osis (NETosis), as well as retinal venular leukoembolization. Notably, heterozygous mice displayed an intermediate phenotype, suggesting a gene dose effect. In vitro studies were performed to study the role of SOCS3 protein levels in the regulation of the inflammatory response. In human umbilical vein endothelial cells, pulse-chase experiments showed that SOCS3 protein had a half-life less than 20 minutes. Inhibition of SOCS3 ubiquitination and proteasomal degradation led to protein accumulation and a stronger inhibition of IL-6 signaling and barrier function loss. Together, our data demonstrate that the regulation of SOCS3 protein levels is critical to inhibit IL-6-mediated endotheliopathy during shock and provide a promising therapeutic avenue to prevent multiorgan dysfunction through stabilization of endothelial SOCS3.
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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.