Ets-1 Is Required for the Activation of VEGFR3 during Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Endothelial Cells

Gutierrez, Kimberley D.; Morris, Valerie; Wu, David; Barcy, Serge; Lagunoff, Michael

doi:10.1128/jvi.03241-12

Cited by 16 publications

(14 citation statements)

References 58 publications

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“…We assessed the transactivation effect of Ets-1 on vascular endothelial growth factors (VEGFRs), which are the direct target genes of Ets-1. 18 , 23 , 24 , 25 , 26 As shown in Figures 3b–d , overexpression of wild-type Ets-1 in MIN6 cells caused a marked increase in the mRNA level of VEGFR2 and VEGFR3, but not of VEGFR1. By contrast, overexpression of Ets-1 ΔTAD (transactivation domain) and Ets-1 ΔETS , two deletion mutants of Ets-1 that cause a loss in transactivation activity and DNA binding activity, respectively, 14 did not show any transactivation effect on the VEGFR2 or VEGFR3 genes, indicating a regulatory effect of Ets-1 on VEGFR gene transcription in MIN6 cells.…”

Section: Resultsmentioning

confidence: 81%

Ets-1 as an early response gene against hypoxia-induced apoptosis in pancreatic β-cells

Qiao

Zhu

et al. 2015

Cell Death Dis

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Hypoxia complicates islet isolation for transplantation and may contribute to pancreatic β-cell failure in type 2 diabetes. Pancreatic β-cells are susceptible to hypoxia-induced apoptosis. Severe hypoxic conditions during the immediate post-transplantation period are a main non-immune factor leading to β-cell death and islet graft failure. In this study, we identified the transcription factor Ets-1 (v-ets erythroblastosis virus E26 oncogene homolog 1) as an early response gene against hypoxia-induced apoptosis in pancreatic β-cells. Hypoxia regulates Ets-1 at multiple levels according to the degree of β-cell oxygen deprivation. Moderate hypoxia promotes Ets-1 gene transcription, whereas severe hypoxia promotes its transactivation activity, as well as its ubiquitin-proteasome mediated degradation. This degradation causes a relative insufficiency of Ets-1 activity, and limits the transactivation effect of Ets-1 on downstream hypoxic-inducible genes and its anti-apoptotic function. Overexpression of ectopic Ets-1 in MIN6 and INS-1 cells protects them from severe hypoxia-induced apoptosis in a mitochondria-dependent manner, confirming that a sufficient amount of Ets-1 activity is critical for protection of pancreatic β-cells against hypoxic injury. Targeting Ets-1 expression may be a useful strategy for islet graft protection during the immediate post-transplantation period.

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Section: Resultsmentioning

confidence: 81%

Ets-1 as an early response gene against hypoxia-induced apoptosis in pancreatic β-cells

Qiao

Zhu

et al. 2015

Cell Death Dis

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“…Currently, the leading theory is that Kaposi’s sarcoma is a tumour originating from the endothelium of the blood vessels that are most commonly associated with Kaposi’s sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) infection [ 1 ] [ 10 ] [ 11 ]. It is believed that it is this virus that is the cause of a change in the differentiation and the function of the endothelial cells, resulting in the appearance of altered vascular structures to a lymphatic phenotype and determining the angioproliferative character of KS [ 1 ] [ 12 ]. A possible explanation for this mechanism is that this occurs with the involvement of VEGFR3-lymphatic endothelial-cell-specific receptor important for lymphangiogenesis [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is believed that it is this virus that is the cause of a change in the differentiation and the function of the endothelial cells, resulting in the appearance of altered vascular structures to a lymphatic phenotype and determining the angioproliferative character of KS [ 1 ] [ 12 ]. A possible explanation for this mechanism is that this occurs with the involvement of VEGFR3-lymphatic endothelial-cell-specific receptor important for lymphangiogenesis [ 12 ]. It is considered that the transcription factor Its-1 activates the promoter of VEGFR3 and thus he plays a role in KSHV activation of endothelial cells during latent KSHV infection [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

A Series of Patients with Kaposi Sarcoma (Mediterranean/Classical Type): Case Presentations and Short Update on Pathogenesis and Treatment

Temelkova¹,

Tronnier²,

Terziev³

et al. 2018

Open Access Maced J Med Sci

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BACKGROUND:Kaposi’s sarcoma was first described in 1872 by Moritz Kaposi. To date, it is considered a malignant disease is originating from the endothelial cells of the lymphatic vessels believed to be infected with HHV-8. The current classification defines four major epidemiological forms of Kaposi’s sarcoma: classical, endemic, AIDS-associated, and iatrogenic.CASE REPORT:A 90-year-old male is presented with multiple plaques- and tumour-shaped brown-violet formations located on an erythematous-livid base in the area of both feet and both shanks. Two samples were taken from the lesions on the skin of the shanks, with histopathological examination and the subsequent immunohistochemistry showing Kaposi’s sarcoma.CONCLUSIONS:Kaposi sarcoma is a disease that causes difficulties both in diagnostic and therapeutic respect. The only sure way to determine the correct diagnosis is immunohistochemical staining with the anti-HHV8 antibody. Despite the wide range of systematic and local treatment options, there is still no unified algorithm and a unified strategy for the treatment of Kaposi’s sarcoma.

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“…Recent studies have shown that the KS herpes virus can infect endothelial cells of blood vessels and reprogram the neoplastic HHV8-infected endothelial cells to lymphatic endothelium. The tumour cells show induction of lymphatic lineage-specific genes, including Prox1 and downregulation of blood vascular genes [ 68 , 69 ]. Angiosarcomas.…”

Section: Lymphatic Differentiation In Tumours and Tumour-like Lesionsmentioning

confidence: 99%

Lymph vessels: the forgotten second circulation in health and disease

et al. 2016

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The lymphatic circulation is still a somewhat forgotten part of the circulatory system. Despite this, novel insights in lymph angiogenesis in health and disease, application of immune markers for lymphatic growth and differentiation and also the introduction of new imaging techniques to visualize the lymphatic circulation have improved our understanding of lymphatic function in both health and disease, especially in the last decade. These achievements yield better understanding of the various manifestations of lymph oedemas and malformations, and also the patterns of lymphovascular spread of cancers. Immune markers that recognize lymphatic endothelium antigens, such as podoplanin, LYVE-1 and Prox-1, can be successfully applied in diagnostic pathology and have revealed (at least partial) lymphatic differentiation in many types of vascular lesions.Electronic supplementary materialThe online version of this article (doi:10.1007/s00428-016-1945-6) contains supplementary material, which is available to authorized users.

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Ets-1 Is Required for the Activation of VEGFR3 during Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Endothelial Cells

Cited by 16 publications

References 58 publications

Ets-1 as an early response gene against hypoxia-induced apoptosis in pancreatic β-cells

Ets-1 as an early response gene against hypoxia-induced apoptosis in pancreatic β-cells

A Series of Patients with Kaposi Sarcoma (Mediterranean/Classical Type): Case Presentations and Short Update on Pathogenesis and Treatment

Lymph vessels: the forgotten second circulation in health and disease

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