Open AccessExpression and Cellular Distribution of Vascular Endothelial Growth Factor‐C System in Cortical Tubers of the Tuberous Sclerosis Complex
Author(s) -
Zhang ChunQing,
Shu HaiFeng,
Yin Qing,
An Ning,
Xu SenLin,
Yin JinBo,
Song YeChun,
Liu ShiYong,
Yang Hui
Publication year - 2012
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2011.00519.x
Subject(s) - tuberous sclerosis , immunostaining , pathogenesis , biology , vascular endothelial growth factor , in situ hybridization , microbiology and biotechnology , downregulation and upregulation , signal transduction , receptor , cortex (anatomy) , cancer research , pathology , neuroscience , messenger rna , immunohistochemistry , immunology , medicine , gene , vegf receptors , genetics
Cortical tubers are malformations of cortical development in patients with tuberous sclerosis complex (TSC), and highly associated with pediatric intractable epilepsy. Recent evidence has shown that signaling mediated through vascular endothelial growth factor‐C (VEGF‐C) and its receptors, VEGFR‐2 and VEGFR‐3, has direct effects on both neurons and glial cells. To understand the potential role of VEGF‐C system in the pathogenesis of cortical tubers, we investigated the expression patterns of VEGF‐C signaling in cortical tubers compared with age‐matched normal control cortex (CTX). We found that VEGF‐C, VEGFR‐2 and VEGFR‐3 were clearly upregulated in tubers at both the mRNA and protein levels, compared with CTX. The in situ hybridization and immunostaining results demonstrated that VEGF‐C, VEGFR‐2 and VEGFR‐3 were highly expressed in dysplastic neurons (DNs), giant cells (GCs) and reactive astrocytes within tubers. Most DNs/GCs expressing VEGF‐C and its receptors co‐labeled with neuronal rather than astrocytic markers, suggesting a neuronal lineage. In addition, protein levels of Akt‐1, p‐Bad and ERK1/2, the important downstream factors of the VEGF‐C pathway, were significantly increased in cortical tubers, indicating involvement of VEGF‐C–dependent prosurvival signaling in cortical tubers. Taken together, our results suggest a putative role for the VEGF‐C signaling pathway in the pathogenesis of cortical tubers.