Src contributes to IL6-induced vascular endothelial growth factor-C expression in lymphatic endothelial cells

Huang, Yu Jie; Yang, Hung-Yu; Hsu, Ya Fen; Chiu, Pei Ting; Ou, George; Hsu, Ming Jen

doi:10.1007/s10456-013-9386-1

Cited by 41 publications

(53 citation statements)

References 70 publications

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“…C/EBP β and c-Fos are potent inducers of neovascularization in various diseases3839. A recent study showed that C/EBP β bound to the promoter region of VEGF-C to induce VEGF-C expression in IL-6-exposed lymphatic endothelial cells16. Lee et al 40.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies demonstrated that the activity of C/EBP β, c-Fos and HIF-1αis also regulated by posttranslational modification caused by phosphorylation by different kinases, such as MAPK, cdc2, PKA and PKC1617484950. Previous studies targeted the effects of ERK1/2 pathways on GPR91-dependent VEGF expression in the retinas of streptozotocin-induced diabetic rats7.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of C/EBPs is regulated at multiple levels through the action of numerous factors, including hormones, mitogens, cytokines, nutrients and certain toxins12. Recent studies demonstrated roles for C/EBP β and C/EBP δ in the regulation of VEGF-C expression1516. Extracellular regulated protein kinases 1/2 (ERK1/2) is the upstream signal that enhances the binding of C/EBPβ to the promoter region of VEGF-C16.…”

mentioning

confidence: 99%

“…Recent studies demonstrated roles for C/EBP β and C/EBP δ in the regulation of VEGF-C expression1516. Extracellular regulated protein kinases 1/2 (ERK1/2) is the upstream signal that enhances the binding of C/EBPβ to the promoter region of VEGF-C16.…”

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confidence: 99%

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Transcription factors regulate GPR91-mediated expression of VEGF in hypoxia-induced retinopathy

Gao

et al. 2017

Sci Rep

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Hypoxia is the most important factor in the pathogenesis of diabetic retinopathy (DR). Our previous studies demonstrated that G protein-coupled receptor 91(GPR91) participated in the regulation of vascular endothelial growth factor (VEGF) secretion in DR. The present study induced OIR model in newborn rats using exposure to alternating 24-hour episodes of 50% and 12% oxygen for 14 days. Treatment with GPR91 shRNA attenuated the retinal avascular area, abnormal neovascularization and pericyte loss. Western blot and qRT-PCR demonstrated that CoCl2 exposure promoted VEGF expression and secretion, activated the ERK1/2 signaling pathways and upregulated C/EBP and AP-1. Knockdown of GPR91 inhibited ERK1/2 activity. GPR91 siRNA transduction and the ERK1/2 inhibitor U0126 inhibited the increases in C/EBP β, C/EBP δ, c-Fos and HIF-1α. Luciferase reporter assays and a chromatin immunoprecipitation (ChIP) assay demonstrated that C/EBP β and c-Fos bound the functional transcriptional factor binding site in the region of the VEGF promoter, but not C/EBP δ. Knockdown of C/EBP β and c-Fos using RNAi reduced VEGF expression. Our data suggest that activation of the GPR91-ERK1/2-C/EBP β (c-Fos, HIF-1α) signaling pathway plays a tonic role in regulating VEGF transcription in rat retinal ganglion cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Transcription factors regulate GPR91-mediated expression of VEGF in hypoxia-induced retinopathy

Gao

et al. 2017

Sci Rep

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“…For example, a significant correlation between IL-6 protein and VEGF-C mRNA with lymph node metastasis in human oral squamous cell carcinoma has been demonstrated [113]. Moreover, in vitro experiments revealed that IL-6 induces VEGF-C expression in human oral squamous cell carcinoma cell line [113] and VEGF-C expression in IL-6 treated murine LECs [114]. …”

Section: Extracellular Matrix (Ecm) With Cancer-associated Fibroblmentioning

confidence: 99%

Impact of the Prolymphangiogenic Crosstalk in the Tumor Microenvironment on Lymphatic Cancer Metastasis

Schlereth

Refaian

Iden

et al. 2014

BioMed Research International

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Lymphangiogenesis is a very early step in lymphatic metastasis. It is regulated and promoted not only by the tumor cells themselves, but also by cells of the tumor microenvironment, including cancer associated fibroblasts, mesenchymal stem cells, dendritic cells, or macrophages. Even the extracellular matrix as well as cytokines and growth factors are involved in the process of lymphangiogenesis and metastasis. The cellular and noncellular components influence each other and can be influenced by the tumor cells. The knowledge about mechanisms behind lymphangiogenesis in the tumor microenvironmental crosstalk is growing and offers starting points for new therapeutic approaches.

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Pregnancy Programming and Preeclampsia: Identifying a Human Endothelial Model to Study Pregnancy-Adapted Endothelial Function and Endothelial Adaptive Failure in Preeclamptic Subjects

Boeldt

Hankes

Alvarez

et al. 2014

Advances in Fetal and Neonatal Physiology

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We have previously reported that the increase in vasodilator production in an ovine model pregnancy is underpinned by an increase in connexin 43 (Cx43) gap junction function, so allowing more uterine artery endothelial cells to produce a more sustained Ca(2+) burst response to agonist stimulation. Since activation of endothelial nitric oxide synthase (eNOS) requires elevated [Ca(2+)]i, it follows that the direct result of enhanced bursting in turn is an increase in nitric oxide (NO) production per cell from more cells, and for a longer period of time. Preeclampsia (PE) is associated with endothelial vasodilatory dysfunction, and the endocrine profile of women with PE includes an increase in a number of factors found in wound sites. The common action of these growth factors and cytokines in wound sites is to mediate Cx43 dysfunction through kinase phosphorylation and closure. Translational studies are now needed to establish if inhibitory phosphorylation of Cx43 in human endothelium is the cause of endothelial dysfunction in PE subjects and if so, to identify the kinase pathways best targeted for therapy in PE subjects. Consistent with this we have already shown endothelial Ca(2+) and NO responses of human umbilical vein from normal subjects are similar to that of ovine pregnant uterine artery, and that those same responses in cords from PE subjects are blunted to levels more typical of nonpregnant uterine artery. In this review we summarize the further evidence that growth factors and cytokines may indeed mediate endothelial dysfunction in PE subjects through closure of Cx43 gap junctions. We also consider how we may clinically translate our studies to humans by using intact umbilical vein and isolated HUVEC in primary culture for an initial screen of drugs to prevent deleterious Cx43 phosphorylation, with the ultimate goal of reversing PE-related endothelial dysfunction.

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Src contributes to IL6-induced vascular endothelial growth factor-C expression in lymphatic endothelial cells

Cited by 41 publications

References 70 publications

Transcription factors regulate GPR91-mediated expression of VEGF in hypoxia-induced retinopathy

Transcription factors regulate GPR91-mediated expression of VEGF in hypoxia-induced retinopathy

Impact of the Prolymphangiogenic Crosstalk in the Tumor Microenvironment on Lymphatic Cancer Metastasis

Pregnancy Programming and Preeclampsia: Identifying a Human Endothelial Model to Study Pregnancy-Adapted Endothelial Function and Endothelial Adaptive Failure in Preeclamptic Subjects

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