Ninjurin1 is expressed in myeloid cells and mediates endothelium adhesion in the brains of EAE rats

Ahn, Bum Ju; Hj, Lee; Shin, Min Wook; Choi, Jeong-Hyun; Jeong, Joo‐Won; Kim, Kyu‐Won

doi:10.1016/j.bbrc.2009.07.019

Cited by 48 publications

(54 citation statements)

References 19 publications

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“…Thus, these results show that Ninjurin1 is expressed in leukocytes and in inflamed endothelial cells (strong/abundant expression in myeloid-lineage cells and weak/partial expression in the lymphoid-lineage cells). These results are consistent with previous findings (16,18,19).…”

Section: Ninjurin1 Is Up-regulated In the Myeloid Cells And Inflamed supporting

confidence: 94%

“…Finally, because Ninjurin1 was also detected in various other cell types, including neurons, oligodendrocytes, and astrocytes in the CNS (14,16), an investigation of the coordinated interactions between Ninjurin1-expressing cells under inflammation will be helpful when seeking to understand CNS diseases. The growing evidence suggests that many diseases share inflammation as a convergent downstream signal after injury despite the divergent initial triggers (33).…”

Section: Discussionmentioning

confidence: 99%

“…The 12 residues, from Pro 26 to Asn 37 , on the N-terminal ectodomain of Ninjurin1 are critical for its homophilic binding (15). Our group previously reported that Ninjurin1 is preferentially expressed in myeloid cells and in the inflamed endothelium in the EAE rat brain and that its overexpression promotes the adhesion of leukocytes onto endothelial cell monolayers in vitro (16,17). Consistent with our results, Ifergan et al (18) demonstrated that Ninjurin1 is restricted to endothelial cells and myeloid cells, particularly to dendritic cells at lesions from human brains with multiple sclerosis.…”

Section: Ninjurin1 Is a Homotypic Adhesion Molecule That Contributes mentioning

confidence: 97%

“…This result indicates that the weak limb paralysis of EAE in Ninjurin1 KO mice mainly stems from the leukocyte-promoting demyelination regardless of the basal motor function with normal appearance. (15,16,18) and up-regulated in T lymphocytes (19) to promote their recruitment toward inflammatory sites. We, therefore, compared the number of leukocytes that infiltrated into the spinal cords of WT or Ninjurin1 KO mice with EAE.…”

Section: Ninjurin1 Mutant Mice Attenuate the Susceptibility Of Mog 35mentioning

confidence: 99%

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Ninjurin1 Deficiency Attenuates Susceptibility of Experimental Autoimmune Encephalomyelitis in Mice

Ahn¹,

Le²,

Shin³

et al. 2014

Journal of Biological Chemistry

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Background: Effect of Ninjurin1 deletion in the experimental autoimmune encephalomyelitis (EAE) mice has not been examined. Results: Ninjurin1 knock-out (KO) mice are resistance to EAE due to a defect of leukocyte recruitment into lesion sites. Conclusion: Ninjurin1 is a potent target molecule for treating inflammatory diseases such as multiple sclerosis. Significance: Our study proved contribution of Ninjurin1 in EAE pathogenesis in vivo and supports the importance of its targeting strategies.

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Section: Ninjurin1 Is Up-regulated In the Myeloid Cells And Inflamed supporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Ninjurin1 Is a Homotypic Adhesion Molecule That Contributes mentioning

confidence: 97%

Section: Ninjurin1 Mutant Mice Attenuate the Susceptibility Of Mog 35mentioning

confidence: 99%

See 2 more Smart Citations

Ninjurin1 Deficiency Attenuates Susceptibility of Experimental Autoimmune Encephalomyelitis in Mice

Ahn¹,

Le²,

Shin³

et al. 2014

Journal of Biological Chemistry

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“…Ninj1 is an adhesion molecule that is essential for cell-cell interactions; 8 for instance, it is expressed in myeloid cells, including macrophages and monocytes, and mediates adhesion between these and ECs. 37 Therefore, Ninj1 may contribute to vascular stability and maturation by mediating the interaction between PC and EC tubes (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

Ninjurin1 Is a Novel Factor to Regulate Angiogenesis Through the Function of Pericytes

Matsuki

Kabara

Saito

et al. 2015

Circ J

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Background: Capillary pericytes (cPCs), the mural cells of microvessels, play an important role in the formation and maintenance of microvessels; however, little is known about the mechanisms of how cPCs regulate angiogenesis. To identify factors that modulate cPC function, genes whose levels were altered in cPCs during neovessel formation were identified through a microarray screen. Methods and Results:Ninjurin1 (nerve injury-induced protein, Ninj1) was selected as a candidate factor for angiogenesis regulation. Ninj1 was expressed in capillary cells including endothelial cells (cECs) and was expressed at a higher level in cPCs. Hypoxia induced the gene expression of Ninj1 in addition of vascular endothelial growth factor (VEGF) in cPCs. When cPCs were co-incubated with a thoracic aorta in a three-dimensional Matrigel system, the length of the EC-tubes sprouting from the aorta was increased. Small interfering RNA-mediated downregulation of Ninj1 in cPCs enhanced these cPCs-mediated angiogenic effects, whereas overexpression of Ninj1 attenuated their effects. The production of angiogenic growth factors, such as VEGF and angiopoietin 1, by cPCs was enhanced by the downregulation of Ninj1, and reduced by the overexpression of Ninj1. also determined. EC Tube Formation Angiogenesis AssayThe EC tube formation assay was performed as previously described. 14 A 40-μl volume of growth factor-reduced Matirgel was added to each well of a 96-well plate at room temperature. The gel was solidified at 37°C for at least 30 min and then seeded with 1×10 4 cells/well in 100 μl medium (EBM2 with 2% FBS and 10 ng/ml VEGF). The assay was performed in a CO2 incubator, with plates incubated at 37°C for 24 h. Images were obtained by phase contrast microscopy and the length of the tube-like structure in each well was measured at 40× magnification. Hind Limb Ischmia Surgery and ImmunocytochemistryMale C57BL/6 mice 12 weeks of age were used for experiments. All animal protocols were approved by the Animal Care and Use Committee of Asahikawa Medical University. Unilateral hindlimb ischemia (HLI) models were established by ligation and excision of the femoral artery/vein as previously described. 16 At predetermined time points, mice were sacrificed by overdose with a pentobarbital-based euthanasia solution (200 mg/kg by intraperitoneal injection). Gastrocnemius muscle samples were collected and stored at −80°C for quantitative polymerase chain reaction (qPCR) analysis. The histological assessment of ischemic limb tissue was performed 14 days after hindlimb surgery. Functional vessels were stained by injecting 300 μl phosphate-buffered saline (PBS) containing rhodamine-labeled G. simplicifolia lectin I (100 μg/ml, Vector Laboratories) via the tail vein. After 5 min, mice were sacrificed and perfused through the heart with PBS followed by 4% paraformaldehyde in PBS, and the gastrocnemius muscle was dissected and embedded in Tissue-Tek OCT medium. Ninj1 expression in 10-μm cross-sections was detected by immunocytochemistry using an anti-Ninj1 ...

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NINJ1 Facilitates Abdominal Aortic Aneurysm Formation via Blocking TLR4‐ANXA2 Interaction and Enhancing Macrophage Infiltration

Wu,

Xu,

et al. 2024

Advanced Science

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Abdominal aortic aneurysm (AAA) is a common and potentially life‐threatening condition. Chronic aortic inflammation is closely associated with the pathogenesis of AAA. Nerve injury‐induced protein 1 (NINJ1) is increasingly acknowledged as a significant regulator of the inflammatory process. However, the precise involvement of NINJ1 in AAA formation remains largely unexplored. The present study finds that the expression level of NINJ1 is elevated, along with the specific expression level in macrophages within human and angiotensin II (Ang II)‐induced murine AAA lesions. Furthermore, Ninj1flox/flox and Ninj1flox/floxLyz2‐Cre mice on an ApoE−/− background are generated, and macrophage NINJ1 deficiency inhibits AAA formation and reduces macrophage infiltration in mice infused with Ang II. Consistently, in vitro suppressing the expression level of NINJ1 in macrophages significantly restricts macrophage adhesion and migration, while attenuating macrophage pro‐inflammatory responses. Bulk RNA‐sequencing and pathway analysis uncover that NINJ1 can modulate macrophage infiltration through the TLR4/NF‐κB/CCR2 signaling pathway. Protein‐protein interaction analysis indicates that NINJ1 can activate TLR4 by competitively binding with ANXA2, an inhibitory interacting protein of TLR4. These findings reveal that NINJ1 can modulate AAA formation by promoting macrophage infiltration and pro‐inflammatory responses, highlighting the potential of NINJ1 as a therapeutic target for AAA.

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Ninjurin1 is expressed in myeloid cells and mediates endothelium adhesion in the brains of EAE rats

Cited by 48 publications

References 19 publications

Ninjurin1 Deficiency Attenuates Susceptibility of Experimental Autoimmune Encephalomyelitis in Mice

Ninjurin1 Deficiency Attenuates Susceptibility of Experimental Autoimmune Encephalomyelitis in Mice

Ninjurin1 Is a Novel Factor to Regulate Angiogenesis Through the Function of Pericytes

NINJ1 Facilitates Abdominal Aortic Aneurysm Formation via Blocking TLR4‐ANXA2 Interaction and Enhancing Macrophage Infiltration

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