Upregulation of Vascular Endothelial Growth Factor Receptor-3 in the Spinal Cord of Lewis Rats with Experimental Autoimmune Encephalomyelitis

Abstract

We investigated the spatiotemporal expression of vascular endothelial growth factor receptor–3 (VEGFR-3) in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. VEGFR-3 mRNA and protein were constitutively expressed in gray matter neurons and in a few white matter astrocytes. Induction of VEGFR-3 occurred predominantly in perivascular infiltrated macrophages in the spinal cord white matter during the inductive phase of EAE. VEGFR-3 expression was also induced in activated microglial cells in the gray and white matter, mainly in the peak phase. In addition, reactive astrocytes in the white matter, but not in the gray matter, expressed VEGFR-3 as disease severity increased. These data suggest that VEGFR-3 is involved in the recruitment of monocytic macrophages and in glial reactions during EAE.

Endothelin‐1 increases the expression of VEGF‐R1/Flt‐1 receptors in rat cultured astrocytes through ETB receptors

“…; Park et al . ). The up‐regulations in VEGF receptor subtypes suggest that actions of VEGF signals on astrocytes become prominent in the damaged brain.…”

“…For example, increased expressions of astrocytic VEGF-R1 and -R2 receptors were observed after ischemia and traumatic injury in animal models (Krum and Rosenstein 1998;Choi et al 2007a,b;Wang et al 2005). Increased expression of astrocytic VEGF-R3 was observed after brain ischemia and neuroinflammatory injury (Shin et al 2008;Park et al 2013). The up-regulations in VEGF receptor subtypes suggest that actions of VEGF signals on astrocytes become prominent in the damaged brain.…”

“…; Park et al . ). Together with the increases in VEGF ligands, up‐regulations of VEGF receptor subtypes suggest that regulation of astrocytic functions by VEGF signals becomes more prominent in neurologic disorders.…”

Korean Red Ginseng mitigates spinal demyelination in a model of acute multiple sclerosis by downregulating p38 mitogen-activated protein kinase and nuclear factor-κB signaling pathways

“…The decrease in expression of IL-6, IFN-γ, and COX-2 is in accordance with results of previous reports [26] , [39] . IGF-1, TGF-β, and VEGF-1 are growth factors known to be expressed in most neurodegenerative diseases [40] , [41] , [42] . However, they are not widely studied in MS or EAE.…”

“…Defects in TGF-β expression and its signaling in T cells are correlated with the onset of EAE [43] . VEGF-1 is involved in the recruitment of monocytic macrophages and glial reactions during EAE [42] . Ginsenosides (Rg5, Rd, and Rb1) can regulate the expression of IGF-1 in streptozotocin-induced memory impaired rats [44] and the expression of TGF-β in liver fibrosis around hepatic stellate cells [45] .…”