Affinage

ROBO4

Roundabout homolog 4 · UniProt Q8WZ75

Length
1007 aa
Mass
107.5 kDa
Annotated
2026-06-10
93 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ROBO4 is an endothelial cell-specific transmembrane receptor that stabilizes the vasculature by restraining pathologic angiogenesis and vascular hyperpermeability (PMID:18345009, PMID:19855388). Its barrier-protective output converges on suppression of VEGF/VEGFR2 signaling: Slit2-activated ROBO4 blocks Src-family kinase activation, and loss of ROBO4 in the presence of angiogenic stimuli enhances VEGFR2-Src-FAK signaling and vessel density (PMID:18345009, PMID:20498081). A central effector arm is the ROBO4-paxillin complex, which recruits the Arf-GAP GIT1 to inactivate Arf6 and downstream Rac1, suppressing protrusive activity, neovascularization, and leak; ROBO4 acts upstream of the ARF6-VEGF axis (PMID:19855388, PMID:40778968). Strikingly, the cytoplasmic domain is dispensable for barrier and anti-angiogenic functions, which instead operate through extracellular binding to the Netrin receptor UNC5B to counteract VEGFR2-Y949/Y951 phosphorylation (PMID:21238923, PMID:27882935). ROBO4 additionally stabilizes endothelial junctions through a TRAF7 interaction that protects VE-cadherin and through an IQGAP1-TRAF7 trimeric complex that promotes IQGAP1 ubiquitination to limit RAC1-driven PTGS2/COX-2 expression, dampening inflammatory vascular responses (PMID:30510113, PMID:38762541). ROBO4 signaling preserves the endothelial barrier in sepsis, influenza, and SARS-CoV-2 models and opposes endothelial-to-mesenchymal transition (PMID:20375003, PMID:36634143, PMID:38383474), and it directs hematopoietic stem cell niche localization and trafficking in bone marrow (PMID:21211783, PMID:25640759). Endothelial-specific ROBO4 expression is driven by SP1 and the ETS factor GABP, and is further controlled by promoter demethylation and protein-level stabilization (PMID:17495228, PMID:29618782). ROBO4 loss-of-function variants link the gene to bicuspid aortic valve and thoracic aortic aneurysm via impaired barrier function and EndMT (PMID:30455415).

Mechanistic history

Synthesis pass · year-by-year structured walk · 34 steps
  1. 2003 Medium

    Established ROBO4 as an endothelium-restricted member of the Robo family and posed whether it transduces Slit-Robo guidance signals like its paralogs.

    Evidence Immunoprecipitation and heterologous migration assays reporting Slit binding and Mena interaction

    PMID:12941633

    Open questions at the time
    • Slit binding reported here was subsequently disputed
    • Mena interaction not functionally dissected downstream
  2. 2004 Medium

    Resolved whether ROBO4 is a direct Slit receptor and demonstrated its soluble ectodomain is anti-angiogenic, decoupling ROBO4's vascular function from canonical Slit binding.

    Evidence BiaCore and immunoprecipitation binding assays plus in vivo sponge/aortic ring angiogenesis models

    PMID:15486058

    Open questions at the time
    • Did not identify the true activating ligand
    • Mechanism of soluble ectodomain inhibition unresolved
  3. 2006 Medium

    Linked ROBO4 to Rho-family GTPase signaling, providing a cytoskeletal mechanism for its control of endothelial behavior.

    Evidence Gain-of-function overexpression and zebrafish morpholino knockdown with Rho GTPase activation assays

    PMID:16481322

    Open questions at the time
    • Direction of GTPase modulation later contested by Arf6/Rac1-suppression models
    • Adaptors linking ROBO4 to GTPases not identified here
  4. 2008 High

    Defined the core barrier-stabilizing function: Slit2-ROBO4 counters VEGF-driven migration, permeability, and pathologic angiogenesis by blocking Src activation, with ROBO4 knockout worsening disease.

    Evidence In vitro permeability/tube assays, Src kinase activity readouts, and Robo4-/- retinal/choroidal disease models

    PMID:18345009

    Open questions at the time
    • Intracellular adaptors transmitting the anti-Src signal not yet defined
    • Relationship to GTPase signaling unresolved at this stage
  5. 2008 Medium

    Identified actin-nucleating partners and a Robo1-ROBO4 heterodimer requirement, connecting the receptor to filopodial cytoskeletal output.

    Evidence Yeast two-hybrid, GST pulldown, co-IP, and siRNA-based filopodia imaging

    PMID:18948384

    Open questions at the time
    • Functional significance of WASP/N-WASP/WIP binding in vivo unclear
    • Heterodimer requirement not reconciled with later Robo1-independent models
  6. 2009 High

    Built the central effector module: ROBO4-paxillin recruits GIT1 to inactivate Arf6 then Rac1, mechanistically explaining suppression of protrusion and leak.

    Evidence Reciprocal co-IP, Arf6 activity assays, and in vivo Arf6-inhibition phenocopy in disease models

    PMID:19855388

    Open questions at the time
    • How extracellular signals trigger paxillin recruitment not defined
    • Integration with VEGFR2/Src arm not fully mapped
  7. 2010 High

    Extended ROBO4 barrier function to systemic vascular crises, showing Slit2-ROBO4 protects against cytokine-storm-driven leak and improves survival.

    Evidence Mouse endotoxemia, polymicrobial sepsis, and H5N1 influenza models with permeability and survival readouts

    PMID:20375003

    Open questions at the time
    • Molecular link between TLR/cytokine signaling and ROBO4 not detailed here
  8. 2010 High

    Genetically dissected ROBO4 versus Robo1 in suppressing VEGFR2-Src-FAK signaling, establishing mural-cell Slit acts through endothelial ROBO4.

    Evidence Conditional/germline Robo4 and Robo1 knockouts with VEGFR2/Src/FAK phosphorylation assays

    PMID:20498081

    Open questions at the time
    • Receptor-proximal events controlling VEGFR2 phosphorylation not resolved
  9. 2011 High

    Identified UNC5B as a direct ROBO4 extracellular partner mediating barrier maintenance, redefining the relevant ligand/co-receptor for vascular function.

    Evidence Ectodomain interaction screen, co-IP, blocking antibodies, and UNC5B-dependent Robo4-/- rescue

    PMID:21238923

    Open questions at the time
    • Stoichiometry and structure of ROBO4-UNC5B complex unknown
    • How UNC5B engagement feeds into intracellular effectors unclear
  10. 2011 High

    Revealed a non-vascular-barrier role: ROBO4 anchors HSCs to bone marrow niches and cooperates with CXCR4 for niche access.

    Evidence Robo4 knockout with transplantation, homing, and CXCR4 expression analyses

    PMID:21211783

    Open questions at the time
    • Whether HSC role is cell-intrinsic or endothelial-niche-mediated not separated here
  11. 2011 High

    Demonstrated ROBO4 functions in CNS neuronal radial migration via Slit-dependent and Slit-independent modes, broadening its biology beyond endothelium.

    Evidence In utero electroporation knockdown, conditional knockout, Boyden chamber and growth cone collapse assays

    PMID:22123939

    Open questions at the time
    • Neuronal effectors of ROBO4 not identified
    • Relationship to endothelial signaling machinery unclear
  12. 2012 Medium

    Clarified and partly contradicted the HSC reconstitution model, showing ROBO4 is required for homing and mobilization but not long-term self-renewal.

    Evidence Robo4-/- homing, competitive transplantation, and G-CSF mobilization assays

    PMID:23226403

    Open questions at the time
    • Discrepancy with prior reconstitution defect unresolved
    • Single-lab germline KO
  13. 2012 Medium

    Connected ROBO4 to junctional integrity at the molecular level, linking its loss to tight-junction protein downregulation and LIMK/cofilin activation.

    Evidence siRNA knockdown in retinal endothelial cells with permeability, junction protein, and pathway readouts

    PMID:23163536

    Open questions at the time
    • Direct mechanism linking ROBO4 to occludin/ZO-1 not established
  14. 2013 Medium

    Defined an anti-inflammatory ROBO4 arm that represses TLR4-Pyk2-NF-kB signaling, contrasting with pro-inflammatory Robo1.

    Evidence siRNA knockdown with cytokine ELISA, ICAM-1, monocyte adhesion, and NF-kB/Pyk2 phosphorylation assays

    PMID:24272999

    Open questions at the time
    • Direct biochemical link between ROBO4 and Pyk2 not shown
  15. 2013 Medium

    Established SLIT3 as a functional ligand promoting ROBO4-dependent vascular network formation, indicating context-dependent pro-angiogenic outputs.

    Evidence siRNA knockdown of SLIT3/ROBO4 with 3D network imaging and in vivo xenogenic implant

    PMID:24090675

    Open questions at the time
    • Reconciliation of pro- vs anti-angiogenic ROBO4 outputs unresolved
  16. 2013 Medium

    Extended ROBO4 anti-angiogenic signaling to lymphatics, showing Slit2-N triggers VEGFR-3 internalization and PI3K/Akt blockade via ROBO4.

    Evidence Robo4 siRNA with proliferation/migration/tube assays, VEGFR-3 internalization, and PI3K/Akt blotting

    PMID:24708522

    Open questions at the time
    • Mechanism of ROBO4-driven VEGFR-3 internalization not detailed
  17. 2015 Medium

    Showed ROBO4 governs directional HSC trafficking across vessel walls, integrating barrier function with stem cell transit.

    Evidence Robo4 KO with induced permeability and directional HSC trafficking assays

    PMID:25640759

    Open questions at the time
    • Molecular machinery of directional transmigration not defined
  18. 2015 Medium

    Demonstrated ROBO4 suppresses Slit2/Robo1-driven migration intracellularly rather than by ligand competition, and identified CdGAP as a Robo1 partner.

    Evidence Boyden chamber migration, siRNA dissection, co-IP, and targeted proteomics

    PMID:26713366

    Open questions at the time
    • Intracellular mechanism of ROBO4-Robo1 crosstalk not fully mapped
  19. 2016 High

    Proved the cytoplasmic domain is dispensable for barrier and anti-angiogenic function, which instead requires UNC5B-mediated suppression of VEGFR2-Y949/Y951.

    Evidence Robo4ΔCD transgenic mice in OIR and wound models with VEGFR2 phosphorylation and UNC5B epistasis

    PMID:27882935

    Open questions at the time
    • How ectodomain-only ROBO4 transmits signal to VEGFR2 mechanistically unresolved
    • Reconciliation with cytoplasmic paxillin/Arf6 module needed
  20. 2017 Medium

    Identified β3 integrin sequestration of ROBO4 as a VEGF-driven mechanism reducing ROBO4 function in diabetic cerebral neovascularization.

    Evidence Co-IP, VEGFR-2 inhibitor, ROBO4 overexpression, and diabetic rat model

    PMID:28116460

    Open questions at the time
    • Direct binding interface not mapped
    • Single-lab finding
  21. 2017 Medium

    Confirmed the Slit2-ROBO4-paxillin-Rac1 axis operates at the blood-brain barrier in injury, establishing paxillin dependence in vivo.

    Evidence siRNA epistasis of Robo4/paxillin, Rac1 pulldown, and Evans blue BBB assay in surgical brain injury

    PMID:28389649

    Open questions at the time
    • Apparent Rac1 activation here vs Rac1 suppression in other models not reconciled
  22. 2018 Medium

    Linked ROBO4 loss-of-function variants to bicuspid aortic valve and thoracic aortic aneurysm through impaired barrier function and EndMT.

    Evidence ROBO4 silencing and mutant expression in endothelial lines with barrier and transcriptome analysis

    PMID:30455415

    Open questions at the time
    • Causal mechanism from EndMT to valve/aneurysm pathology not demonstrated in vivo
  23. 2018 Medium

    Identified Annexin A2 as an extracellular ROBO4 ligand feeding the paxillin-ARF6 pathway to reduce cerebrovascular permeability.

    Evidence Co-IP, knockdown, ARF6 activity, permeability assays, and ANXA2 KO mice

    PMID:29786451

    Open questions at the time
    • Specificity of ANXA2 vs UNC5B/Slit ligands not compared
    • Single-lab co-IP
  24. 2018 Medium

    Defined epigenetic control of endothelial ROBO4 expression via ETV2 recruitment of TET1/TET2 to demethylate the proximal promoter.

    Evidence Co-IP, reporter assays, bisulfite sequencing, and iPS-to-EC differentiation

    PMID:29618782

    Open questions at the time
    • In vivo requirement of ETV2-TET axis for ROBO4 not tested
  25. 2019 Medium

    Identified the ROBO4-TRAF7 junctional module that stabilizes VE-cadherin to suppress TNFα-induced hyperpermeability.

    Evidence Co-IP, C-terminal deletion, gain/loss-of-function, VE-cadherin localization, and Robo4-/- endotoxemia model

    PMID:30510113

    Open questions at the time
    • Whether TRAF7 E3 activity is required not resolved here
  26. 2019 Medium

    Revealed ROBO4 expression on lymphatic sinus endothelium controls B cell egress, expanding its immune trafficking roles.

    Evidence Robo4 KO with lymphocyte flow cytometry, homing assays, and sinus endothelial microarray

    PMID:31772321

    Open questions at the time
    • Molecular mechanism of ROBO4-mediated B cell egress unknown
  27. 2021 Medium

    Showed HDAC3 sustains ROBO4 transcription by maintaining GABP, identifying a chromatin regulator upstream of barrier function.

    Evidence Isoform-specific HDAC siRNA, MS-275 inhibition, GABP analysis, and permeability assays

    PMID:33955828

    Open questions at the time
    • Direct HDAC3 action on GABP locus not fully demonstrated
  28. 2022 Medium

    Defined post-translational control of ROBO4 surface levels by ADAM10/17 shedding, generating a soluble Slit3-inhibitory decoy buffered by ligand-induced endocytosis.

    Evidence ADAM inhibitors and siRNA, shedding and endocytosis assays, and Slit3 angiogenesis assays

    PMID:35288626

    Open questions at the time
    • Physiological role of soluble ROBO4 in vivo not established
  29. 2023 High

    Mapped TGF-β superfamily control of ROBO4, with ALK5-SMAD2/3 inducing and ALK1-SMAD1/5 repressing it, and validated ROBO4 induction as protective in sepsis and SARS-CoV-2 leak.

    Evidence Small molecule screen, ALK1 inhibitor, endothelial Robo4 transgenic overexpression, and LPS/SARS-CoV-2 models

    PMID:36634143

    Open questions at the time
    • Direct SMAD binding to ROBO4 promoter not detailed
  30. 2024 High

    Defined a ROBO4-IQGAP1-TRAF7 trimeric complex that limits RAC1-driven COX-2/PTGS2, providing a molecular basis for ROBO4's anti-inflammatory action.

    Evidence RNA-seq, co-IP, ubiquitination and RAC1 activity assays, and Robo4-/- inflammatory disease models

    PMID:38762541

    Open questions at the time
    • How extracellular signals trigger the trimeric complex unclear
  31. 2024 Medium

    Showed ROBO4 opposes EndMT and protects hematopoietic reconstitution by restraining Smad and AKT/NF-kB-driven Snail1 activation.

    Evidence Lentiviral knockdown/overexpression with EndMT marker and pathway analysis and EC-HSPC co-culture

    PMID:38383474

    Open questions at the time
    • Direct ROBO4 effectors controlling EndMT pathways not identified
  32. 2024 Medium

    Demonstrated context-dependent, pathologic ROBO4 induction: TET2 demethylation enhances SP1-driven ROBO4 expression under hyperglycemia, reducing tight junctions and driving retinal vascular abnormalities.

    Evidence Bisulfite sequencing, ChIP, shRNA, 5hmC quantification, and diabetic mouse model

    PMID:37430272

    Open questions at the time
    • Mechanism by which elevated ROBO4 lowers ZO-1/occludin not defined
  33. 2024 Medium

    Identified USP5 as a deubiquitinase stabilizing ROBO4 protein, with stabilization promoting high-glucose RPE cell damage.

    Evidence Co-IP, deubiquitination assay, and siRNA/overexpression with viability/apoptosis/ELISA readouts

    PMID:38735506

    Open questions at the time
    • E3 ligase counteracting USP5 not identified
    • Single-lab finding
  34. 2025 Medium

    Confirmed ROBO4 acts upstream of the ARF6-VEGF axis to inhibit pathological retinal angiogenesis via epistatic rescue.

    Evidence Robo4 overexpression/knockdown with ARF6 rescue and OIR mouse model

    PMID:40778968

    Open questions at the time
    • Direct biochemical link from ROBO4 to ARF6/VEGF regulation not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ROBO4 integrates its multiple receptor partners (UNC5B, ANXA2, β3 integrin) with its intracellular effector modules (paxillin-GIT1-Arf6, TRAF7-IQGAP1, VEGFR2-Src) into a unified context-dependent signaling logic, and a structural model of its ligand-engaged complexes, remain unresolved.
  • No structural model of ROBO4 ectodomain complexes
  • Switch between barrier-protective and pathologic outputs not mechanistically defined
  • Apparent opposing effects on Rac1 across studies not reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-168256 Immune System 3
Complex memberships
ROBO4-IQGAP1-TRAF7 complexROBO4-UNC5B complexROBO4-paxillin-GIT1 complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Robo4 is expressed specifically in vascular endothelium and binds Slit ligands (Slit1, Slit2, Slit3) as shown by immunoprecipitation, inhibiting endothelial cell migration. Robo4 also binds the actin regulatory protein Mena (an effector of Robo-Slit signaling) via immunoprecipitation. Immunoprecipitation, heterologous expression migration assay Developmental biology Medium 12941633
2004 Soluble extracellular domain of Robo4 (Robo4Fc) inhibits angiogenesis in vivo and endothelial migration/proliferation in vitro, but Robo4 does NOT bind Slit1, Slit2, or Slit3 as determined by immunoprecipitation and BiaCore analysis (Slits bind Robo1, not Robo4). BiaCore binding assay, immunoprecipitation, rodent sponge angiogenesis model, aortic ring assay, endothelial migration/proliferation assays FASEB journal Medium 15486058
2006 Robo4 activates Cdc42 and Rac1 Rho GTPases in endothelial cells (gain-of-function in vitro), and zebrafish robo4 knockdown reduces active Cdc42 and Rac1, supporting an attraction/guidance signaling mechanism through Rho GTPases. Gain-of-function overexpression, zebrafish morpholino knockdown, Rho GTPase activation assay Journal of Biological Chemistry Medium 16481322
2008 Robo4 binds to Wiskott-Aldrich syndrome protein (WASP), N-WASP, and WASP-interacting protein (WIP) actin-nucleating complex via yeast two-hybrid and GST-pulldown. Robo1 and Robo4 form a heterodimeric complex (co-immunoprecipitation), and Robo1 is required for Robo4-mediated filopodia induction in endothelial cells. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, siRNA knockdown, live-cell imaging of filopodia FASEB journal Medium 18948384
2008 Slit2 activation of Robo4 inhibits VEGF-165-induced endothelial migration, tube formation, and vascular permeability in vitro, and inhibits pathologic angiogenesis and vascular leak in vivo, by blocking Src family kinase activation. Robo4-/- mice show enhanced pathologic angiogenesis and vascular leak. In vitro migration/tube formation/permeability assays, Src kinase activity assay, Robo4 knockout mouse models of retinal/choroidal vascular disease Nature medicine High 18345009
2009 Robo4 directly interacts with the intracellular adaptor paxillin (and its paralogue Hic-5) at the cell surface. Formation of this Robo4-paxillin complex recruits the Arf-GAP GIT1, which inactivates Arf6 and consequently Rac1, thereby suppressing cellular protrusive activity, neovascularization, and vascular hyperpermeability. Inhibition of Arf6 in vivo phenocopies Robo4 activation. Co-immunoprecipitation, biochemical interaction assays, siRNA knockdown, Arf6 activity assay, in vivo choroidal/retinal disease models Nature cell biology High 19855388
2010 Slit2-Robo4 signaling stabilizes the endothelial barrier in response to cytokine storm (LPS, polymicrobial sepsis, H5N1 influenza), reducing vascular permeability in lung and other organs and increasing survival in mouse models. Mouse models of endotoxemia, polymicrobial sepsis, and H5N1 influenza; vascular permeability assays; survival analysis Science translational medicine High 20375003
2010 In the mammary gland, endothelial Robo4 loss combined with angiogenic stimuli leads to enhanced VEGFR2 signaling through Src and FAK kinases, increasing vessel density. Stromal mural-cell-derived Slit signals through endothelial Robo4 (not Robo1) to suppress VEGF/VEGFR2 signaling. Robo4 and Robo1 conditional/germline knockout mice, VEGFR2/Src/FAK phosphorylation assays PNAS High 20498081
2011 Robo4 maintains vessel integrity and inhibits angiogenesis by directly binding to UNC5B (a vascular Netrin receptor) via its extracellular domain. Robo4-UNC5B interaction inhibits signaling downstream of VEGF; soluble Robo4 rescues barrier defects in Robo4-/- mice only when UNC5B is functional. Protein-protein interaction screen with Robo4 extracellular domain, co-immunoprecipitation, function-blocking antibodies, Robo4-/- rescue assays Developmental cell High 21238923
2011 Robo4 functions in hematopoietic stem cells (HSCs) to anchor them to bone marrow niches; Robo4-deficient HSCs show poor BM niche localization and reduced long-term reconstitution. Robo4 cooperates with Cxcr4 for HSC niche access, and Cxcr4 is upregulated in Robo4-/- HSCs to compensate. Robo4 germline knockout mouse, HSC transplantation assays, bone marrow homing assays, CXCR4 expression analysis Cell stem cell High 21211783
2011 Robo4 regulates radial migration of newborn neurons in developing neocortex in a Slit-dependent and Slit-independent manner. Robo4 knockdown in cortical neurons causes severe radial migration defects and misorientation, and increases sensitivity to Slit-mediated repulsion. In utero electroporation with siRNA, Cre-mediated conditional knockout in floxed-Robo4 mice, Boyden chamber migration assay, growth cone collapse assay Cerebral cortex High 22123939
2012 Robo4 deficiency in mice impairs HSC homing to bone marrow and granulocyte-CSF-induced HSC mobilization, but Robo4 is not essential for long-term repopulating capacity or self-renewal of HSCs. Robo4-/- mouse, homing assay, competitive transplantation, G-CSF-induced mobilization assay PloS one Medium 23226403
2012 Robo4 knockdown in human retinal vascular endothelial cells increases monolayer permeability, downregulates tight junction proteins occludin and ZO-1, causes F-actin rearrangement, and activates the LIMK/cofilin pathway. siRNA knockdown, RITC-dextran flux permeability assay, Western blotting, immunofluorescence Current eye research Medium 23163536
2013 Slit2-Robo4 signaling represses LPS-induced endothelial inflammation (cytokine secretion, ICAM-1 upregulation, monocyte adhesion) by inhibiting the Pyk2-NF-κB pathway downstream of TLR4. Robo1 has opposing pro-inflammatory properties and is downregulated by Slit2 via miR-218. siRNA knockdown, cytokine ELISA, ICAM-1 expression assay, monocyte adhesion assay, NF-κB/Pyk2 phosphorylation assays Journal of Immunology Medium 24272999
2013 SLIT3 (secreted by pericytic MSCs) acts as a ligand for ROBO4 on endothelial cells to promote vascular network formation in engineered tissue. siRNA knockdown of ROBO4 in endothelial cells abolishes formation of functional human blood vessels in an in vivo xenogenic implant. siRNA knockdown of SLIT3 and ROBO4, 3D vascular network live imaging, in vivo xenogenic implant assay Journal of molecular and cellular cardiology Medium 24090675
2013 Slit2-N inhibits VEGF-C-mediated lymphatic endothelial cell proliferation, migration, and tube formation in a Robo4-dependent manner, inducing internalization of VEGFR-3 and blocking PI3K/Akt pathway activation. siRNA knockdown of Robo4, cell proliferation/migration/tube formation assays, VEGFR-3 internalization assay, PI3K/Akt Western blotting Cell communication and signaling Medium 24708522
2015 ROBO4 on vascular endothelium actively promotes HSC translocation across vessel walls into bone marrow (extravasation), while vascular integrity mediated by ROBO4 prevents reverse (BM-to-blood) escape of HSCs, thus regulating directionality of HSC trafficking. Robo4 KO mouse, induced vascular permeability experiments, HSC trafficking directional assays Stem cell reports Medium 25640759
2016 The cytoplasmic domain of Robo4 is dispensable for preventing vascular permeability and inhibiting neovascularization. Robo4 and a truncated cytoplasmic-domain-deleted Robo4 (Robo4ΔCD) both counteract VEGFR2-Y949 (Y951 in human) phosphorylation by signaling through UNC5B; Robo4 does not affect Slit2 signaling in this context. Transgenic mice expressing Robo4ΔCD, oxygen-induced retinopathy model, wound healing model, VEGFR2 phosphorylation assays, UNC5B signaling epistasis Nature communications High 27882935
2018 ROBO4 variants (loss-of-function) in endothelial cells result in impaired barrier function and a gene expression profile consistent with endothelial-to-mesenchymal transition (EndMT), identifying an endothelial mechanism for bicuspid aortic valve and thoracic aortic aneurysm. ROBO4 silencing and mutant ROBO4 expression in endothelial cell lines; barrier function assay; transcriptome analysis Nature genetics Medium 30455415
2018 Annexin A2 (ANXA2) acts as an extracellular ligand for Robo4 and modulates the Robo4-paxillin-ARF6 signaling pathway to reduce trans-endothelial permeability in cerebrovascular injury. ANXA2 also interacts with F-actin and VE-cadherin. Co-immunoprecipitation, knockdown assays, ARF6 activity assay, trans-endothelial permeability assay, ANXA2 KO mice Journal of cerebral blood flow and metabolism Medium 29786451
2018 ETV2, an ETS family transcription factor, directly interacts with TET1 and TET2 (methylcytosine-converting enzymes) via immunoprecipitation. ETV2-TET1/TET2 complexes demethylate the Robo4 proximal promoter at ETS motifs, inducing endothelial cell-specific Robo4 expression during differentiation. Co-immunoprecipitation, adenoviral overexpression, reporter assay, bisulfite sequencing of CpG methylation, iPS-to-EC differentiation assay Scientific reports Medium 29618782
2019 Robo4 interacts with TRAF7 (an E3 ubiquitin ligase) through the C-terminus of Robo4. The Robo4-TRAF7 complex suppresses TNFα-induced endothelial hyperpermeability by stabilizing VE-cadherin at cell junctions; TRAF7 is required for Robo4-mediated permeability suppression. Co-immunoprecipitation, deletion assays (Robo4 C-terminus), gain/loss-of-function experiments, VE-cadherin localization assay, Robo4-/- mouse endotoxemia model Journal of cell science Medium 30510113
2019 Robo4 contributes to the turnover of Peyer's patch B cells and is selectively expressed on lymphatic sinus endothelial cells. Robo4-deficient mice accumulate naive B cells in Peyer's patches, demonstrating a role in B cell egress through efferent lymphatics. Robo4 KO mouse, lymphocyte flow cytometry, short-term homing assays, microarray of sinus endothelial cells Mucosal immunology Medium 31772321
2022 Robo4 is constitutively shed from the endothelial cell surface by ADAM10 and ADAM17 metalloproteinases. The resulting soluble Robo4 inhibits angiogenic Slit3 signaling. Slit3 ligand itself induces Robo4 endocytosis, shielding it from shedding and thereby enhancing membrane Robo4 signaling. ADAM inhibitors and siRNA knockdown of ADAM10/17, shedding assays, Robo4 endocytosis assay, Slit3-induced angiogenesis assay Scientific reports Medium 35288626
2023 ALK5-SMAD2/3 signaling positively and ALK1-SMAD1/5 signaling negatively regulate Robo4 expression. Endothelial-specific Robo4 overexpression suppresses vascular permeability and reduces mortality in LPS-treated mice; ALK1 inhibitor increases Robo4 expression and suppresses SARS-CoV-2-induced endothelial barrier disruption. Small molecule screening, ALK1 inhibitor treatment, endothelial-specific Robo4 transgenic overexpression mice, LPS endotoxemia model, SARS-CoV-2 infection model, permeability assays PNAS High 36634143
2024 ROBO4 interacts with IQGAP1 and TRAF7 (E3 ubiquitin ligase) in a trimeric complex. Within this complex, ROBO4 enhances IQGAP1 ubiquitination through TRAF7, inhibiting prolonged RAC1 activation and thereby decreasing PTGS2/COX-2 expression in inflammatory endothelial cells. RNA-seq, co-immunoprecipitation, ubiquitination assay, RAC1 activity assay, Robo4-/- mouse inflammatory disease models (arthritis, edema, pain) Communications biology High 38762541
2024 TET2-mediated active demethylation of the ROBO4 promoter (oxidizing 5-methylcytosine to 5-hydroxymethylcytosine) under hyperglycemia enhances SP1 binding to the ROBO4 promoter, increases ROBO4 expression, and decreases ZO-1 and occludin, leading to retinal vascular abnormalities. TET2 or ROBO4 inhibition ameliorates these defects. Bisulfite sequencing, ChIP assay, shRNA knockdown of TET2 and ROBO4, 5hmC quantification, permeability/migration/angiogenesis assays, streptozotocin diabetic mouse model Journal of translational medicine Medium 37430272
2024 USP5 stabilizes ROBO4 protein via deubiquitination. USP5 and ROBO4 interact as shown by co-IP and deubiquitination assay. USP5-mediated ROBO4 stabilization promotes high-glucose-induced retinal pigment epithelial cell damage (promoting apoptosis, inflammation, oxidative stress). Co-immunoprecipitation, deubiquitination assay, siRNA/overexpression of USP5 and ROBO4, cell viability/apoptosis/ELISA assays Cellular signalling Medium 38735506
2024 Robo4 depletion in endothelial cells increases expression of endoglin (CD105) and promotes EndMT via canonical (Smad) and non-canonical (AKT/NF-κB) pathways, activating Snail1 nuclear translocation. Robo4 overexpression upregulates ICAM-1 and VCAM-1 and inhibits irradiation-induced EndMT, protecting hematopoietic reconstitution. Lentiviral RNAi and gene overexpression, Western blotting for EndMT markers, Smad/AKT/NF-κB pathway analysis, co-culture of ECs and HSPCs, flow cytometry Cell death & disease Medium 38383474
2007 The 3-kb human Robo4 promoter drives endothelial cell-specific expression via SP1 binding motifs at -42 and -153 and an ETS (GABP) binding site at -119. GABP and SP1 transcription factors bind these motifs (confirmed by EMSA, supershift antibodies, and ChIP). siRNA knockdown of GABP or SP1 reduces endogenous Robo4 mRNA by ~50%. Deletion/mutation reporter assays, EMSA with supershift, ChIP, siRNA knockdown, Hprt-targeted LacZ knock-in mice Circulation research High 17495228
2017 In the brain vasculature, ROBO4 interacts with β3 integrin (co-immunoprecipitation); VEGF-activated β3 integrin sequesters ROBO4, reducing its expression and function during diabetes-induced cerebral neovascularization. VEGFR-2 inhibition increases ROBO4 expression and reduces ROBO4-β3 integrin interaction. Co-immunoprecipitation, VEGFR-2 inhibitor (SKLB1002), ROBO4 overexpression in brain, diabetic rat model (GK rats), immunohistochemistry Diabetologia Medium 28116460
2017 Slit2 treatment via Robo4 increases Rac1 activity (measured by pulldown) in the context of surgical brain injury, and this effect is reversed by siRNA knockdown of Robo4 or paxillin, reducing blood-brain barrier permeability. siRNA knockdown of Robo4 and paxillin, Rac1 activity pulldown assay, BBB permeability assay (Evans blue), rodent surgical brain injury model Scientific reports Medium 28389649
2015 Robo4 suppresses Slit2/Robo1-mediated HUVEC migration through an intracellular (not extracellular competitive) mechanism. CdGAP (a Rac1/Cdc42-specific GTPase activating protein) was identified as a Robo1 signaling partner by co-immunoprecipitation, linking Slit2/Robo1 to cytoskeletal regulation. Boyden chamber migration assay, siRNA knockdown of Robo4 and Robo1, co-immunoprecipitation of Robo1 and CdGAP, targeted proteomics Biochemical and biophysical research communications Medium 26713366
2021 HDAC3 maintains Robo4 expression in endothelial cells by sustaining GABP transcription factor expression. Knockdown of HDAC3 (but not HDAC1 or HDAC2) decreases Robo4 expression; the HDAC inhibitor MS-275 suppresses Robo4 via HDAC3/GABP axis, increasing endothelial permeability. siRNA knockdown of individual HDACs, MS-275 pharmacological inhibition, GABP expression analysis, transendothelial electrical resistance, Evans blue assay in mice Tissue barriers Medium 33955828
2025 Robo4 inhibits pathological angiogenesis in OIR by negatively regulating ARF6 and VEGF expression. Robo4 overexpression reduces ARF6 and VEGF levels; Robo4 knockdown increases ARF6 and VEGF. ARF6 overexpression partially reverses Robo4-mediated inhibition of angiogenesis, confirming Robo4 acts upstream of ARF6 in the ARF6-VEGF axis. Robo4 overexpression and siRNA knockdown, ARF6 overexpression rescue experiment, VEGF/ARF6 Western blotting, oxygen-induced retinopathy mouse model Human cell Medium 40778968

Source papers

Stage 0 corpus · 93 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability. Nature medicine 321 18345009
2010 Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza. Science translational medicine 281 20375003
2003 Robo4 is a vascular-specific receptor that inhibits endothelial migration. Developmental biology 269 12941633
2009 Slit2-Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nature cell biology 196 19855388
2011 Robo4 maintains vessel integrity and inhibits angiogenesis by interacting with UNC5B. Developmental cell 174 21238923
2004 Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell migration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 146 15486058
2018 ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm. Nature genetics 119 30455415
2011 Robo4 cooperates with CXCR4 to specify hematopoietic stem cell localization to bone marrow niches. Cell stem cell 107 21211783
2008 Active involvement of Robo1 and Robo4 in filopodia formation and endothelial cell motility mediated via WASP and other actin nucleation-promoting factors. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 101 18948384
1972 Cell wall peptidoglycan mutants of Escherichia coli K-12: existence of two clusters of genes, mra and mrb, for cell wall peptidoglycan biosynthesis. Journal of bacteriology 81 4563986
2013 Slit2-Robo4 pathway modulates lipopolysaccharide-induced endothelial inflammation and its expression is dysregulated during endotoxemia. Journal of immunology (Baltimore, Md. : 1950) 80 24272999
2006 Robo4 signaling in endothelial cells implies attraction guidance mechanisms. The Journal of biological chemistry 71 16481322
2010 Vascular Robo4 restricts proangiogenic VEGF signaling in breast. Proceedings of the National Academy of Sciences of the United States of America 70 20498081
2006 Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer. Oncology reports 66 16685377
2007 A three-kilobase fragment of the human Robo4 promoter directs cell type-specific expression in endothelium. Circulation research 65 17495228
2013 SLIT3-ROBO4 activation promotes vascular network formation in human engineered tissue and angiogenesis in vivo. Journal of molecular and cellular cardiology 55 24090675
2020 Esaxerenone, a novel nonsteroidal mineralocorticoid receptor blocker (MRB) in hypertension and chronic kidney disease. Journal of human hypertension 49 32661269
2016 The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization. Nature communications 47 27882935
2015 ROBO4-mediated vascular integrity regulates the directionality of hematopoietic stem cell trafficking. Stem cell reports 43 25640759
2019 Enhanced ROBO4 is mediated by up-regulation of HIF-1α/SP1 or reduction in miR-125b-5p/miR-146a-5p in diabetic retinopathy. Journal of cellular and molecular medicine 39 31094072
2019 Regulatory mechanisms of Robo4 and their effects on angiogenesis. Bioscience reports 39 31160487
2011 Robo4 regulates the radial migration of newborn neurons in developing neocortex. Cerebral cortex (New York, N.Y. : 1991) 39 22123939
2011 Robo4-dependent Slit signaling stabilizes the vasculature during pathologic angiogenesis and cytokine storm. Current opinion in hematology 38 21423011
2015 Endothelial Robo4 suppresses breast cancer growth and metastasis through regulation of tumor angiogenesis. Molecular oncology 37 26778715
2008 A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo. Blood 36 18519813
2014 Role of ROBO4 signalling in developmental and pathological angiogenesis. BioMed research international 33 24689049
2018 Annexin A2 is a Robo4 ligand that modulates ARF6 activation-associated cerebral trans-endothelial permeability. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 32 29786451
2014 Slit2N and Robo4 regulate lymphangiogenesis through the VEGF-C/VEGFR-3 pathway. Cell communication and signaling : CCS 31 24708522
2012 Slit2/Robo4 signaling modulates HIV-1 gp120-induced lymphatic hyperpermeability. PLoS pathogens 31 22241990
2010 MR angiogenesis imaging with Robo4- vs. alphaVbeta3-targeted nanoparticles in a B16/F10 mouse melanoma model. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 20585027
2009 Expression of Robo4 in the fibrovascular membranes from patients with proliferative diabetic retinopathy and its role in RF/6A and RPE cells. Molecular vision 29 19495426
2019 The Robo4-TRAF7 complex suppresses endothelial hyperpermeability in inflammation. Journal of cell science 27 30510113
2018 ETV2-TET1/TET2 Complexes Induce Endothelial Cell-Specific Robo4 Expression via Promoter Demethylation. Scientific reports 26 29618782
2017 Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes. Diabetologia 26 28116460
2013 Robo4 is an effective tumor endothelial marker for antibody-drug conjugates based on the rapid isolation of the anti-Robo4 cell-internalizing antibody. Blood 26 23365463
2018 Slit2/Robo4 axis may contribute to endothelial cell dysfunction and angiogenesis disturbance in systemic sclerosis. Annals of the rheumatic diseases 25 30021803
2017 Endothelial Robo4 regulates IL-6 production by endothelial cells and monocytes via a crosstalk mechanism in inflammation. Biochemical and biophysical research communications 24 29137978
2017 Recombinant Slit2 Reduces Surgical Brain Injury Induced Blood Brain Barrier Disruption via Robo4 Dependent Rac1 Activation in a Rodent Model. Scientific reports 21 28389649
2015 Suppression of Slit2/Robo1 mediated HUVEC migration by Robo4. Biochemical and biophysical research communications 21 26713366
2019 Upregulated VEGF and Robo4 correlate with the reduction of miR-15a in the development of diabetic retinopathy. Endocrine 19 30980286
2013 Slit2-Robo4 receptor responses inhibit ANDV directed permeability of human lung microvascular endothelial cells. Antiviral research 19 23702092
2024 Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases. Communications biology 18 38762541
2014 Robo4 vaccines induce antibodies that retard tumor growth. Angiogenesis 18 25348086
2008 Robo1/robo4: different expression patterns in retinal development. Experimental eye research 18 19084519
2023 OncoTherad® (MRB-CFI-1) Nanoimmunotherapy: A Promising Strategy to Treat Bacillus Calmette-Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer: Crosstalk among T-Cell CX3CR1, Immune Checkpoints, and the Toll-Like Receptor 4 Signaling Pathway. International journal of molecular sciences 17 38139364
2023 Upregulation of Robo4 expression by SMAD signaling suppresses vascular permeability and mortality in endotoxemia and COVID-19 models. Proceedings of the National Academy of Sciences of the United States of America 16 36634143
2021 HDAC inhibitor, MS-275, increases vascular permeability by suppressing Robo4 expression in endothelial cells. Tissue barriers 16 33955828
2021 Salidroside Prevents Hypoxia-Induced Human Retinal Microvascular Endothelial Cell Damage Via miR-138/ROBO4 Axis. Investigative ophthalmology & visual science 12 34269814
2016 Increased expression of Slit2 and its receptors Robo1 and Robo4 in reactive astrocytes of the rat hippocampus after transient forebrain ischemia. Brain research 12 26764532
2012 Robo4 plays a role in bone marrow homing and mobilization, but is not essential in the long-term repopulating capacity of hematopoietic stem cells. PloS one 12 23226403
2024 The Role of SLIT3-ROBO4 Signaling in Endoplasmic Reticulum Stress-Induced Delayed Corneal Epithelial and Nerve Regeneration. Investigative ophthalmology & visual science 11 38700874
2023 The role of TET2-mediated ROBO4 hypomethylation in the development of diabetic retinopathy. Journal of translational medicine 11 37430272
2014 Raised plasma Robo4 and cardiac surgery-associated acute kidney injury. PloS one 11 25360813
2009 Functionally defining the endothelial transcriptome, from Robo4 to ECSCR. Biochemical Society transactions 11 19909249
2023 Robo4 inhibits gamma radiation-induced permeability of a murine microvascular endothelial cell by regulating the junctions. Cellular & molecular biology letters 10 36647012
2022 OncoTherad® (MRB-CFI-1) nano-immunotherapy reduced tumoral progression in non-muscle invasive bladder cancer through activation of Toll-like signaling pathway. Tissue & cell 10 35245856
2022 Robo4 is constitutively shed by ADAMs from endothelial cells and the shed Robo4 functions to inhibit Slit3-induced angiogenesis. Scientific reports 10 35288626
2019 MicroRNA-411 plays a protective role in diabetic retinopathy through targeted regulating Robo4. European review for medical and pharmacological sciences 10 31773667
2018 Slit2/Robo4 signaling pathway modulates endothelial hyper-permeability in a two-event in vitro model of transfusion-related acute lung injury. Blood cells, molecules & diseases 10 30846360
2012 Effect of Robo4 on retinal endothelial permeability. Current eye research 10 23163536
2019 miR-204 Negatively Regulates Cell Growth And Metastasis By Targeting ROBO4 In Human Bladder Cancer. OncoTargets and therapy 9 31802889
2015 Expression of the Robo4 receptor in endothelial cells is regulated by two AP-1 protein complexes. Biochemical and biophysical research communications 9 26459591
2021 Aminophylline modulates the permeability of endothelial cells via the Slit2-Robo4 pathway in lipopolysaccharide-induced inflammation. Experimental and therapeutic medicine 8 34373728
2021 Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1. PloS one 7 34388149
2017 Slit2/Robo4 Signaling: Potential Role of a VEGF-Antagonist Pathway to Regulate Luteal Permeability. Geburtshilfe und Frauenheilkunde 7 28190892
2024 Endothelial Robo4 suppresses endothelial-to-mesenchymal transition induced by irradiation and improves hematopoietic reconstitution. Cell death & disease 6 38383474
2024 USP5 facilitates diabetic retinopathy development by stabilizing ROBO4 via deubiquitination. Cellular signalling 5 38735506
2022 Mechanism of TLR4 mediated immune effect in transfusion-induced acute lung injury based on Slit2/Robo4 signaling pathway. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 5 35853810
2020 ROBO4 deletion ameliorates PAF-mediated skin inflammation via regulating the mRNA translation efficiency of LPCAT1/LPCAT2 and the expression of PAF receptor. International journal of biological sciences 5 32140075
2020 DS-7080a, a Selective Anti-ROBO4 Antibody, Shows Anti-Angiogenic Efficacy with Distinctly Different Profiles from Anti-VEGF Agents. Translational vision science & technology 5 32879763
2019 Deletion of Robo4 prevents high-fat diet-induced adipose artery and systemic metabolic dysfunction. Microcirculation (New York, N.Y. : 1994) 5 30825241
2024 Slit2-Robo4 signal pathway and tight junction in intestine mediate LPS-induced inflammation in mice. European journal of medical research 4 38937814
2022 BML-111 alleviates inflammatory response of alveolar epithelial cells via miR-494/Slit2/Robo4 signalling axis to improve acute lung injury. Autoimmunity 4 35656971
2019 Inhibitory Effect of Slit2-N on VEGF165-induced proliferation of vascular endothelia via Slit2-N-Robo4-Akt pathway in choroidal neovascularization. Cell cycle (Georgetown, Tex.) 4 31081721
2019 Robo4 contributes to the turnover of Peyer's patch B cells. Mucosal immunology 4 31772321
2019 Expression of HIF-1α and Robo4 in the retinas of streptozotocin-induced diabetic mice. International journal of clinical and experimental pathology 4 31933855
2012 [Transcriptional regulation of the endothelial cell-specific receptor, Robo4]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 4 23023422
2024 Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad® (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases. Medical oncology (Northwood, London, England) 3 39404781
2020 PRC2 Components Maintain DNA Hypermethylation of the Upstream Promoter and Regulate Robo4 Expression in Endothelial Cells. Biological & pharmaceutical bulletin 3 32238717
2013 [Myocardial Slit2/Robo4 expression and impact of exogenous Slit2 on proliferation and migration of cardiac microvascular endothelial cells]. Zhonghua xin xue guan bing za zhi 3 24524607
2008 Ligand-independent assembly of purified soluble magic roundabout (Robo4), a tumor-specific endothelial marker. Protein expression and purification 3 18571431
2025 Clinical and immunohistochemical effects of OncoTherad (MRB-CFI-1) nanoimmunotherapy on SERBP1, HABP4, CD44 and Ki-67 in BCG-unresponsive non-muscle invasive bladder cancer. Tissue & cell 1 39938427
2024 A novel serous ovarian carcinoma model induced by DMBA: Results from OncoTherad® (MRB-CFI-1) immunotherapy preclinical testing. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 1 39693910
2022 Binding and Efficacy of Anti-Robo4 CAR-T Cells against Solid Tumors. Biomedicines 1 35740295
2020 Withdrawal Notice: Molecular Mechanism of TLR4 Mediated T Cell Immune Effect in Transfusion-induced Acute Lung Injury based on Slit2/Robo4 Signaling Pathway. Current molecular pharmacology 1 33030140
2026 Congenital Coarctation of the Aorta in a Patient With ROBO4 c.695C>T (p.Thr232Met) Germline Variant. Annals of internal medicine. Clinical cases 0 41613935
2026 Leveraging in-silico deep learning and computational analyses to predict the pathogenicity of ROBO4 variants of uncertain significance in aortic aneurysm and dissection patients. BMC cardiovascular disorders 0 41639767
2026 Assessing the Safety and Efficacy of Agonistic Monoclonal Antibody against Robo4 versus Ranibizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Phase I, Open-Label, Multicenter Study. Ophthalmology science 0 42064470
2026 Regulation of H-type angiogenesis and permeability in the subchondral bone of osteoarthritis: the role of Slit3 and the Robo4/Rac1-GTP/ROS axis. Frontiers in cell and developmental biology 0 42148297
2026 Deletion of Robo4 worsens neuroinflammation in a mouse model of Alzheimer's disease. Physiological reports 0 42237690
2025 Robo4 inhibits neovascularization in oxygen-induced retinopathy by regulating ARF6 and VEGF. Human cell 0 40778968
2024 A great diversity of ROBO4 expression and regulations identified by data mining and transgene mice. Gene expression patterns : GEP 0 39181524
2022 [The destructive role of soluble Robo4 secreted by the M1-polarized-microglia during cerebral ischemia-reperfusion in blood-brain barrier integrity]. Sheng li xue bao : [Acta physiologica Sinica] 0 35993202

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