Expression and Cellular Distribution of Vascular Endothelial Growth Factor‐C System in Cortical Tubers of the Tuberous Sclerosis Complex

Zhang, Chunqing; Shu, Hai-Feng; Yin, Qian; An, Ning; Xu, Senlin; Yin, Jie; Song, Yechun; Liu, Shiyong; Yang, Hui

doi:10.1111/j.1750-3639.2011.00519.x

Cited by 18 publications

(17 citation statements)

References 49 publications

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“…Our data demonstrated the induction of VEGFR-3 protein, but not its ligand, in reactive astrocytes at the graft site. These results agree well with previous findings that VEGFR-3 induction in reactive astrocytes is a generalized phenomenon during CNS lesions Shin et al 2010;Shin et al 2008;Zhang et al 2012). However, they contrast with the finding of astroglial induction of VEGF-C mRNA in the post-ischemic hippocampus (Shin et al 2008).…”

Section: Discussionsupporting

confidence: 93%

Expression of Vascular Endothelial Growth Factor-C (VEGF-C) and Its Receptor (VEGFR-3) in the Glial Reaction Elicited by Human Mesenchymal Stem Cell Engraftment in the Normal Rat Brain

Shin

Riew

Park

et al. 2014

J Histochem Cytochem.

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To determine whether vascular endothelial growth factor-C (VEGF-C) and its receptor (VEGFR-3) are involved in the glial reaction elicited by transplanted mesenchymal stem cells (MSCs), we examined the cellular localization of VEGF-C and VEGFR-3 proteins in the striatum of adult normal rats that received bone marrow-derived human MSCs. The MSC grafts were infiltrated with activated microglia/macrophages and astrocytes over a 2-week period post-transplantation, which appeared to parallel the loss of transplanted MSCs. VEGF-C/VEGFR-3 was expressed in activated microglia/macrophages recruited to the graft site, where the induction of VEGF-C protein was rather late compared with that of its receptor. VEGF-C protein was absent or very weak on day 3, whereas VEGFR-3 immunoreactivity was evident within the first three days. Furthermore, within three days, VEGF-C could be detected in the brain macrophages localized immediately adjacent to the needle track. At the same time, almost all the brain macrophages in both regions expressed VEGFR-3. Reactive astrocytes at the graft site expressed VEGFR-3, but not VEGF-C. These data demonstrated the characteristic time- and cell-dependent expression patterns for VEGF-C and VEGFR-3 within the engrafted brain tissue, suggesting that they may contribute to neuroinflammation in MSC transplantation, possibly through the recruitment and/or activation of microglia/macrophages and astrogliosis.

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Section: Discussionsupporting

confidence: 93%

Expression of Vascular Endothelial Growth Factor-C (VEGF-C) and Its Receptor (VEGFR-3) in the Glial Reaction Elicited by Human Mesenchymal Stem Cell Engraftment in the Normal Rat Brain

Shin

Riew

Park

et al. 2014

J Histochem Cytochem.

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“…When a disagreement occurred, independent reevaluation was performed by both observers to define the final score. A semi-quantitative analysis was performed as previously described [ 38 , 39 ]. Using a Leica DMIRB microscope to examine a total microscopic area of 781.250 μm 2 (200 high-power non-overlapping fields of 0.0625 × 0.0625 mm width, using a square grid inserted into the eyepiece) in each section.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of CD47 and CD200 in patients with focal cortical dysplasia type IIb and tuberous sclerosis complex

Sun

Zhang

Chen

et al. 2016

J Neuroinflammation

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BackgroundFocal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are well-recognized causes of chronic intractable epilepsy in children. Accumulating evidence suggests that activation of the microglia/macrophage and concomitant inflammatory response in FCD IIb and TSC may contribute to the initiation and recurrence of seizures. The membrane glycoproteins CD47 and CD200, which are highly expressed in neurons and other cells, mediate inhibitory signals through their receptors, signal regulatory protein α (SIRP-α) and CD200R, respectively, in microglia/macrophages. We investigate the levels and expression pattern of CD47/SIRP-α and CD200/CD200R in surgically resected brain tissues from patients with FCD IIb and TSC, and the potential effect of soluble human CD47 Fc and CD200 Fc on the inhibition of several proinflammatory cytokines associated with FCD IIb and TSC in living epileptogenic brain slices in vitro. The level of interleukin-4 (IL-4), a modulator of CD200, was also investigated.MethodsTwelve FCD IIb (range 1.8–9.5 years), 13 TSC (range 1.5–10 years) patients, and 6 control cases (range 1.5–11 years) were enrolled. The levels of CD47/SIRP-α and CD200/CD200R were assessed by quantitative real-time polymerase chain reaction and western blot. The expression pattern of CD47/SIRP-α and CD200/CD200R was investigated by immunohistochemical analysis, and the cytokine concentrations were measured by enzyme-linked immune-sorbent assays.ResultsBoth the messenger RNA and protein levels of CD47, SIRP-α, and CD200, as well as the mRNA level of IL-4, were downregulated in epileptogenic lesions of FCD IIb and TSC compared with the control specimens, whereas CD200R levels were not significantly changed. CD47, SIRP-α, and CD200 were decreasingly expressed in dysmorphic neuron, balloon cells, and giant cells. CD47 Fc and CD200 Fc could inhibit IL-6 release but did not suppress IL-1β or IL-17 production.ConclusionsOur results suggest that microglial activation may be partially caused by CD47/SIRP-α- and CD200/CD200R-mediated reductions in the immune inhibitory pathways within FCD IIb and TSC cortical lesions where chronic neuroinflammation has been established. Upregulation or activation of CD47/SIRP-α and CD200/CD200R may have therapeutic potential for controlling neuroinflammation in human FCD IIb and TSC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0546-2) contains supplementary material, which is available to authorized users.

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“…VEGF-C, VEGFR-2 and VEGFR-3 are expressed in cortical brain tumours of TSC patients with a history of epileptic seizures [50]. The role of VEGF-C in cortical tubers of TSC may be to regulate epileptic activities through an inflammatory mechanism, rather than via its lymphangiogenic properties in TSC [50].…”

Section: Lymphangioleiomyomatosismentioning

confidence: 99%

“…The role of VEGF-C in cortical tubers of TSC may be to regulate epileptic activities through an inflammatory mechanism, rather than via its lymphangiogenic properties in TSC [50]. A study by Avila et al .…”

Section: Lymphangioleiomyomatosismentioning

confidence: 99%

Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

Glasgow¹,

El–Chemaly²,

Moss³

2012

European Respiratory Review

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The primary function of the lymphatic system is absorbing and transporting macromolecules and immune cells to the general circulation, thereby regulating fluid, nutrient absorption and immune cell trafficking. Lymphangiogenesis plays an important role in tissue inflammation and tumour cell dissemination. Lymphatic involvement is seen in lymphangioleiomyomatosis (LAM) and idiopathic pulmonary fibrosis (IPF). LAM, a disease primarily affecting females, involves the lung (cystic destruction), kidney (angiomyolipoma) and axial lymphatics (adenopathy and lymphangioleiomyoma). LAM occurs sporadically or in association with tuberous sclerosis complex (TSC). Cystic lung destruction results from proliferation of LAM cells, which are abnormal smooth muscle-like cells with mutations in the TSC1 or TSC2 gene. Lymphatic abnormalities arise from infiltration of LAM cells into the lymphatic wall, leading to damage or obstruction of lymphatic vessels. Benign appearing LAM cells possess metastatic properties and are found in the blood and other body fluids. IPF is a progressive lung disease resulting from fibroblast proliferation and collagen deposition. Lymphangiogenesis is associated with pulmonary destruction and disease severity. A macrophage subset isolated from IPF bronchoalveolar lavage fluid (BALF) express lymphatic endothelial cell markers in vitro, in contrast to the same macrophage subset from normal BALF. Herein, we review lymphatic involvement in LAM and IPF.

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Expression and Cellular Distribution of Vascular Endothelial Growth Factor‐C System in Cortical Tubers of the Tuberous Sclerosis Complex

Cited by 18 publications

References 49 publications

Expression of Vascular Endothelial Growth Factor-C (VEGF-C) and Its Receptor (VEGFR-3) in the Glial Reaction Elicited by Human Mesenchymal Stem Cell Engraftment in the Normal Rat Brain

Expression of Vascular Endothelial Growth Factor-C (VEGF-C) and Its Receptor (VEGFR-3) in the Glial Reaction Elicited by Human Mesenchymal Stem Cell Engraftment in the Normal Rat Brain

Downregulation of CD47 and CD200 in patients with focal cortical dysplasia type IIb and tuberous sclerosis complex

Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

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