Ninjurin1 Mediated Cell Adhesion in Inflammatory Processes

Ninjurin1 is a transmembrane cell adhesion protein that orchestrates key steps in immune cell recruitment and activation during inflammation. Initially identified in nerve injury for its homophilic binding that promotes neurite outgrowth, Ninjurin1 is now recognised as a broad regulator of leukocyte extravasation and inflammatory signalling. Its ectodomain mediates firm adhesion of monocytes and macrophages to endothelial cells, facilitating transendothelial migration into affected tissues. Beyond adhesion, structural studies reveal a role in mediating plasma membrane rupture during lytic cell death, linking cell adhesion to the release of inflammatory mediators. The widespread expression of Ninjurin1 in epithelial, endothelial and immune cells underpins its involvement in diverse pathologies, from autoimmune neuroinflammation to intestinal colitis and post-ischaemic injury. Therapeutic targeting of its adhesion interface or proteolytic derivatives shows promise in modulating inflammatory cell trafficking and limiting tissue damage, highlighting Ninjurin1 as a pivotal junction between cellular adhesion dynamics and the orchestration of inflammatory responses.

Research from Nature Portfolio

A twelve-amino-acid peptide derived from the N-terminal adhesion motif of Ninjurin1 has been shown to confer pro-angiogenic effects in endothelial cells and to enhance vessel regrowth following cerebral ischaemia. This peptide directly binds to endogenous Ninjurin1, activating Ang1–Tie2 and downstream AKT pathways to promote endothelial proliferation, migration and tube formation. In vivo administration in a rodent stroke model augments angiogenesis in the peri-infarct region and improves vascular density, suggesting that modulation of Ninjurin1 adhesive interactions can both influence immune cell infiltration and support reparative neovascularisation in inflamed or injured tissues.

Ninjurin1 Mediated Cell Adhesion in Inflammatory Processes publication trend

The graph below shows the total number of articles in ninjurin1 mediated cell adhesion in inflammatory processes across all publications each year (not limited to Nature Index journals).

Technical terms

Technical term: Ninjurin1 – a transmembrane homophilic adhesion protein implicated in immune cell adhesion, migration and membrane dynamics.

Technical term: Homophilic adhesion – the binding of identical adhesion molecules on the surfaces of neighbouring cells, mediating cell–cell attachment.

Technical term: Transendothelial migration – the process by which leukocytes adhere to and traverse the endothelial barrier to enter inflamed or injured tissues.

Technical term: Plasma membrane rupture (PMR) – a form of membrane disruption during lytic cell death that leads to release of intracellular pro-inflammatory contents.

References

1. NINJ1: Bridging lytic cell death and inflammation therapy. Cell Death & Disease (2024).
2. Mechanism of Homophilic Binding Mediated by Ninjurin, a Novel Widely Expressed Adhesion Molecule*. Journal of Biological Chemistry (1997).
3. Ninjurin1 Deficiency Attenuates Susceptibility of Experimental Autoimmune Encephalomyelitis in Mice*. Journal of Biological Chemistry (2013).
4. Ninjurin1 Enhances the Basal Motility and Transendothelial Migration of Immune Cells by Inducing Protrusive Membrane Dynamics*. Journal of Biological Chemistry (2014).
5. Detrimental Role of Nerve Injury-Induced Protein 1 in Myeloid Cells under Intestinal Inflammatory Conditions. International Journal of Molecular Sciences (2020).
6. Ninjurin 1 dodecamer peptide containing the N-terminal adhesion motif (N-NAM) exerts proangiogenic effects in HUVECs and in the postischemic brain. Scientific Reports (2020).