Inhibition of Neogenin Dampens Hepatic Ischemia-Reperfusion Injury

Abstract

These data provide a unique role for Neo1 in the development of hepatic ischemia and reperfusion injury and identified Neo1 as a potential target to prevent liver dysfunction in the future.

Netrin-1 Augments Chemokinesis in CD4+ T Cells In Vitro and Elicits a Proinflammatory Response In Vivo

“…This effect was reported to be mediated in part via its effects on the local infiltration of neutrophils and macrophages (16, 18, 20, 34). However, more recent studies indicate that the expression of pro-migratory neogenin may be critical in the functional outcome of an inflammatory response (25–27, 35, 36). For example, inflammation is reduced in neogenin knockout mice in models of peritonitis, lung injury and ischemia-reperfusion.…”

“…For example, in an atherosclerosis model, Netrin-1 was found to retain macrophages within plaques by inhibiting macrophage emigration from the inflammatory site (5); also Netrin-1 has been found to promote chronic inflammation in adipose tissue (24). Several studies have evaluated Netrin-1 receptor biology using neogenin knockout mice which mount a reduced inflammatory peritonitis reaction (25), have less leukocyte infiltrates and reduced inflammation in models of acute lung injury (26) and ischemia reperfusion injury (27). …”

Immunomodulatory Functions of Neuronal Guidance Proteins

“…The deletion of Neo1 and its functional inhibition resulted in the reduced infiltration of inflammatory cells and reduced tissue injury following hepatic IR injury [71]. This was also observed for the UNC5b receptor.…”

Strategies for Gene Transfer to Vascularized Composite Allografts

“…Transfection of porcine endothelial cells with human CD59 was able to protect the cells from complement-mediated destruction [99]. Baboons transplanted with hearts, derived from CD55 transgenic pigs, were protected from hyperacute rejection [100]. Gene therapy strategies that modify cell surface expression of the transplanted graft to reduce complement-mediated rejection need to be further explored.…”

“…Gene therapy directed at inhibitors of receptors and/or chemokines which allow acute reactive leukocytes (neutrophils, macrophages, and NKs) as well the augmentation of free radial scavengers and certain toll-like receptors (TLR-1 and TLR-4) could reduce the stress of ischemicreperfusion injury on allotransplant organs [100,101].…”