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Review
. 2017 Mar 8:37:6.
doi: 10.1186/s41232-017-0037-6. eCollection 2017.

The roles of RGMa-neogenin signaling in inflammation and angiogenesis

Yuki Fujita  1 , Toshihide Yamashita  1
Affiliations
Review

The roles of RGMa-neogenin signaling in inflammation and angiogenesis

Yuki Fujita et al. Inflamm Regen. .

Abstract

Repulsive guidance molecule (RGM) is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein that has diverse functions in the developing and pathological central nervous system (CNS). The binding of RGM to its receptor neogenin regulates axon guidance, neuronal differentiation, and survival during the development of the CNS. In the pathological state, RGM expression is induced after spinal cord injury, and the inhibition of RGM promotes axon growth and functional recovery. Furthermore, RGM expression is also observed in immune cells, and RGM regulates inflammation and neurodegeneration in autoimmune encephalomyelitis. RGMa induces T cell activation in experimental autoimmune encephalomyelitis (EAE), which is the animal model of multiple sclerosis (MS). RGM is expressed in pathogenic Th17 cells and induces neurodegeneration by binding to neogenin. Angiogenesis is an additional key factor involved in the pathophysiology of EAE. Via neogenin, treatment with RGMa can suppress endothelial tube formation; this finding indicates that RGMa inhibits neovascularization. These observations suggest the feasibility of utilizing the RGMa-neogenin signaling pathway as a therapeutic target to overcome inflammation and neurodegeneration. This review focuses on the molecular mechanisms of inflammation and angiogenesis via RGM-neogenin signaling.

Keywords: Angiogenesis; Immune response; Multiple sclerosis; Neogenin; RGMa.

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Figures

Fig. 1
Fig. 1
RGMa-neogenin signaling mediates autoimmune encephalomyelitis. RGMa in antigen-presenting cells (APCs) binds to neogenin, leading to the activation of CD4+ T cells in both the peripheral and the central nervous systems. Blocking RGMa with a neutralizing antibody diminishes immune responses and ameliorates the severity of EAE
Fig. 2
Fig. 2
RGMa in Th17 cells induces neurodegeneration. RGMa is preferentially expressed in Th17 cells. The association of RGMa with neogenin in neurons induces neurodegeneration through the dephosphorylation of Akt
See this image and copyright information in PMC

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