ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Slit2-Robo4 pathway modulates lipopolysaccharide-induced endothelial inflammation and its expression is dysregulated during endotoxemia.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- The involvement of regulatory non-coding RNAs in sepsis: a systematic review.Critical care (London, England) · 2016Pooled it
- ARF6 inhibition stabilizes the vasculature and enhances survival during endotoxic shock.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- SLIT2 as a key regulator and therapeutic target in liver injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Transcriptomic profiling of porcine duodenal, jejunal, and ileal organoids in response to porcine epidemic diarrhea virus.Journal of animal science and technology · 2026Article
- Slit2-robo signaling regulates angiogenesis and repair following myocardial infarction.Journal of molecular and cellular cardiology · 2026Article
- Myeloid cell genome-wide screen identifies variants associated with Mycobacterium tuberculosis-induced cytokine transcriptional responses.The Journal of clinical investigation · 2025Article
- N-Homocysteinylation of HMGB1/2 Promotes Corpus Cavernosum Endothelial Senescence in Erectile Dysfunction.International journal of biological sciences · 2025Article
- The neurorepellent SLIT2 inhibits LPS-induced proinflammatory signaling in macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- MicroRNAs in Sepsis.Biomedicines · 2024Review
- Slit2-Robo4 signal pathway and tight junction in intestine mediate LPS-induced inflammation in mice.European journal of medical research · 2024Article
- Understanding the pathophysiology of acute critical illness: translational lessons from zebrafish models.Intensive care medicine experimental · 2024Review
- Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS).Respiratory research · 2024Review
- LncRNA/CircRNA-miRNA-mRNA Axis in Atherosclerotic Inflammation: Research Progress.Current pharmaceutical biotechnology · 2024Review
- Mid-old cells are a potential target for anti-aging interventions in the elderly.Nature communications · 2023Article
- Recombinant Slit2 suppresses neuroinflammation and Cdc42-mediated brain infiltration of peripheral immune cells via Robo1-srGAP1 pathway in a rat model of germinal matrix hemorrhage.Journal of neuroinflammation · 2023Article
- ISGylation of NF-κBp65 by SCFArteriosclerosis, thrombosis, and vascular biology · 2023Article
- MiR-126-Loaded Immunoliposomes against Vascular Endothelial Inflammation In Vitro and Vivo Evaluation.Pharmaceutics · 2023Article
- Robo4 inhibits gamma radiation-induced permeability of a murine microvascular endothelial cell by regulating the junctions.Cellular & molecular biology letters · 2023Article
- Role of the SLIT-ROBO signaling pathway in renal pathophysiology and various renal diseases.Frontiers in physiology · 2023Review
- The role of the tumor microenvironment in colorectal cancer and the potential therapeutic approaches.Journal of clinical laboratory analysis · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The secretory protein Slit2 and its receptors Robo1 and Robo4 are considered to regulate mobility and permeability of endothelial cells and other cell types. However, the roles of Slit2 and its two receptors in endothelial inflammatory responses remain to be clarified. In this study, we show that, in primary HUVECs, Slit2 represses LPS-induced secretion of certain inflammatory cytokines/chemokines, cell adhesion molecule ICAM-1 upregulation, and monocyte adhesion. Slit2's anti-inflammatory effect is mediated by its dominant endothelial-specific receptor Robo4. However, the minor receptor Robo1 has proinflammatory properties and is downregulated by Slit2 via targeting of miR-218. Elucidation of molecular mechanism reveals that Slit2 represses inflammatory responses by inhibiting the Pyk2-NF-κB pathway downstream of LPS-TLR4. Further studies reveal that LPS enhances endothelial inflammation by downregulating the anti-inflammatory Slit2 and Robo4 in HUVECs in vitro, as well as in arterial endothelial cells and liver in vivo during endotoxemia. These results suggest that Slit2-Robo4 signaling is important in regulating LPS-induced endothelial inflammation, and LPS, in turn, enhances inflammation by interfering with the expression of the anti-inflammatory Slit2-Robo4 during the disease state. This implies that Slit2-Robo4 is a key regulator of endothelial inflammation, and its dysregulation during endotoxemia is a novel mechanism for LPS-induced vascular pathogenesis.
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