Expression and Cellular Distribution of Vascular Endothelial Growth Factor‐C System in Cortical Tubers of the Tuberous Sclerosis Complex |
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Authors: | Qing Yin Ning An Sen‐Lin Xu Jin‐Bo Yin Ye‐Chun Song Shi‐Yong Liu Hui Yang |
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Institution: | 1. Department of Rehabilitation and Physical Therapy, Southwest Hospital, Chongqing, China.;2. Epilepsy Research Center of PLA, Department of Neurosurgery, Xinqiao Hospital, Chongqing, China.;3. Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, China. |
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Abstract: | 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. |
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Keywords: | cortical tubers pediatric epilepsy receptors tuberous sclerosis complex vascular endothelial growth factor‐C |
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