In mice genetically predisposed to arterial inflammation, a specific peptide called mPN12 reduces the production of a signaling molecule called Cxcl2 in the aorta when it blocks the Ninjurin-1...
Mechanism
Synthesis from 1 study
When Ninjurin-1 builds up in artery walls, it flips on an inflammation switch called NF-κB, which turns up a signal called Cxcl2. That signal then feeds back to keep the switch on, creating a cycle of ongoing inflammation. Stopping Ninjurin-1 breaks this cycle and turns down the inflammation.
Most probable mechanism
When Ninjurin-1 protein builds up in the lining of blood vessels, it triggers a chain reaction that turns on a key inflammation switch called NF-κB. This switch moves into the cell's control center and turns up the production of a signaling molecule called Cxcl2, which attracts more inflammatory cells. This process keeps going because Cxcl2 feeds back to keep the NF-κB switch active, leading to lasting inflammation and damage in the artery wall. Blocking Ninjurin-1 stops this entire cycle, reducing Cxcl2 and calming the inflammation.
Ninjurin-1 protein expression increases in aortic endothelial cells under inflammatory conditions such as lipid accumulation.
Ninjurin-1 directly promotes phosphorylation and activation of the NF-κB p65 subunit, enabling its translocation into the nucleus.
Activated NF-κB binds to regulatory regions of the Cxcl2 gene, increasing its transcription and protein production in endothelial cells.
Cxcl2 protein binds to its receptors on endothelial cells, reactivating NF-κB and creating a self-sustaining inflammatory loop.
Pharmacological inhibition of Ninjurin-1 interrupts this cascade, preventing NF-κB activation and suppressing Cxcl2 expression.
Evidence from Studies
Supporting (1)
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Ninjurin-1 drives atherosclerosis progression via NF-κB/CXCL-8 activation in endothelial cells
Contradicting (0)
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