scholarly journals Uncovering a Key Role of ETS1 on Vascular Abnormality in Glioblastoma

2021 ◽  
Vol 27 ◽  
Author(s):  
Jiefu Tang ◽  
Yaling Li ◽  
Boxuan Liu ◽  
Wei Liang ◽  
Sanbao Hu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Angiogenesis ◽  
Tgfβ Signaling ◽  
Vascular Abnormality ◽  
Expression Of Genes ◽  
Microvascular Proliferation ◽  
Mouse Brain Endothelial Cells ◽  
Key Factor ◽  
Paired Control

Glioblastoma (GBM) is the most aggressive type of brain tumor. Microvascular proliferation and abnormal vasculature are the hallmarks of the GBM, aggravating disease progression and increasing patient morbidity. Here, we uncovered a key role of ETS1 on vascular abnormality in glioblastoma. ETS1 was upregulated in endothelial cells from human tumors compared to endothelial cells from paired control brain tissue. Knockdown of Ets1 in mouse brain endothelial cells inhibited cell migration and proliferation, and suppressed expression of genes associated with vascular abnormality in GBM. ETS1 upregulation in tumor ECs was dependent on TGFβ signaling, and targeting TGFβ signaling by inhibitor decreased tumor angiogenesis and vascular abnormality in CT-2A glioma model. Our results identified ETS1 as a key factor regulating tumor angiogenesis, and suggested that TGFβ inhibition may suppress the vascular abnormality driven by ETS1.

Characterization and Expression of Genes Encoding Superoxide Dismutase in the Oriental Armyworm, Mythimna separata (Lepidoptera: Noctuidae)

2019 ◽  
Vol 112 (5) ◽  
pp. 2381-2388 ◽  
Author(s):  
Hong-Bo Li ◽  
Chang-Geng Dai ◽  
Yong-Fu He ◽  
Yang Hu
Keyword(s):  
Superoxide Dismutase ◽  
Population Density ◽  
Developmental Stages ◽  
Mythimna Separata ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Key Factor ◽  
Important Pest ◽  
Oriental Armyworm

Abstract Superoxide dismutase (SOD) is an antioxidant metalloenzyme that catalyzes the dismutation of the superoxide anion O2− to O2 and H2O2. Many studies have focused on the role of SOD in response to abiotic stress, but its role during biotic stress, such as changes in organismal population density, has rarely been investigated. The oriental armyworm, Mythimna separata, is an economically important pest that exhibits phenotypic changes in response to population density. Solitary and gregarious phases occur at low and high population density, respectively. To examine the role of SODs in response to population density stress, we cloned two genes encoding SOD, MsCuZnSOD and MsMnSOD, and compared their expression in solitary and gregarious phases of M. separata. The MsCuZnSOD and MsMnSOD ORFs were 480 and 651 bp and encoded predicted protein products of 159 and 216 amino acids, respectively. The two SODs contained motifs that are typical of orthologous proteins. Real-time PCR indicated that the two SOD genes were expressed throughout developmental stages and were significantly upregulated in more mature stages of gregarious M. separata. Expression of the two SOD genes in various tissues of sixth-instar larvae was higher in gregarious versus solitary insects. Furthermore, expression of the SOD genes was significantly upregulated in response to crowding in solitary individuals, but suppressed in gregarious insects subjected to isolation. Collectively, these results suggest that population density may be key factor in the induction of SOD genes in M. separata.

Discovery of Side- and Shear-Dependent miRNAs and mRNAs in Human Aortic Valvular Endothelial Cells

2011 ◽  
Author(s):  
Casey J. Holliday ◽  
Randall F. Ankeny ◽  
Hanjoong Jo ◽  
Robert M. Nerem
Keyword(s):  
Endothelial Cells ◽  
Aortic Valve ◽  
Oscillatory Flow ◽  
Expression Profiles ◽  
Flow Conditions ◽  
Expression Of Genes ◽  
Inflammatory Phenotype ◽  
Cardiovascular Pathologies ◽  
Laminar Shear

Aortic valve (AV) disease is diagnosed by severe symptoms, such as calcification, and typically treated by AV replacement and repair surgeries. The mechanism by which AV disease occurs, specifically the role of the endothelium remains relatively unknown. It is known that disease preferentially occurs on the fibrosa, or aortic side, where it is exposed to disturbed, oscillatory flow, whereas the ventricularis, or side facing the left ventricle, experiences pulsatile, laminar shear and remains non-calcified [1, 2]. Research shows that regulation of miRNAs, short nucleotide segments targeting mRNAs, coincides with cardiovascular pathologies [3] though expression profiles of miRNAs and the mRNAs they modulate in human AV endothelial cells (HAVECs) have not been reported. We hypothesize that disturbed flow conditions present on the fibrosa stimulate ECs to modify expression of genes and miRNAs to induce a pro-inflammatory phenotype.

scholarly journals Sirt1 Inhibits Oxidative Stress in Vascular Endothelial Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Weijin Zhang ◽  
Qiaobing Huang ◽  
Zhenhua Zeng ◽  
Jie Wu ◽  
Yaoyuan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Protective Role ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Key Factor ◽  
Antioxidative Stress

The vascular endothelium is a layer of cells lining the inner surface of vessels, serving as a barrier that mediates microenvironment homeostasis. Deterioration of either the structure or function of endothelial cells (ECs) results in a variety of cardiovascular diseases. Previous studies have shown that reactive oxygen species (ROS) is a key factor that contributes to the impairment of ECs and the subsequent endothelial dysfunction. The longevity regulator Sirt1 is a NAD+-dependent deacetylase that has a potential antioxidative stress activity in vascular ECs. The mechanisms underlying the protective effects involve Sirt1/FOXOs, Sirt1/NF-κB, Sirt1/NOX, Sirt1/SOD, and Sirt1/eNOs pathways. In this review, we summarize the most recent reports in this field to recapitulate the potent mechanisms involving the protective role of Sirt1 in oxidative stress and to highlight the beneficial effects of Sirt1 on cardiovascular functions.

scholarly journals CD44 Is Involved in Tumor Angiogenesis; an Activation Antigen on Human Endothelial Cells

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1150-1159 ◽  
Author(s):  
Arjan W. Griffioen ◽  
Marieke J.H. Coenen ◽  
Cora A. Damen ◽  
Sandra M.M. Hellwig ◽  
David H.J. van Weering ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Tumor Angiogenesis ◽  
Umbilical Vein ◽  
Human Endothelial Cells ◽  
Specific Expression ◽  
Cd44 Expression ◽  
Activation Antigen

Abstract CD44 is described to be an activation molecule in a number of different cell types. We investigated the role of CD44 on human endothelial cells (EC) and in tumor angiogenesis. Using flow cytometry we showed that EC from the vasculature of human solid tumors display an enhanced expression of CD44 as compared to EC from normal tissue. This finding was confirmed by immunohistochemical studies on frozen tissue sections. Because tumors are dependent on angiogenesis, the role of angiogenic stimuli in the enhanced CD44 expression was investigated. We found that basic fibroblast growth factor (bFGF ) and vascular endothelial growth factor were able to efficiently upregulate CD44 expression on cultured human EC. The upregulation reached maximal levels after treatment for 3 days with 10 ng/mL bFGF. The physiological impact of this upregulation was shown by the enhanced binding of EC to hyaluronate after pretreatment with bFGF. In a next set of studies that were designed to unravel the regulation of CD44 expression on EC we concluded that CD44 is an activation antigen on human EC since (1) human umbilical vein derived endothelial cells, which in vivo do not express CD44, begin to express CD44 when plated and cultured, (2) CD44 expression is enhanced after subculture of confluent cultures, (3) CD44 is predominantly expressed on the BrdU incorporating subset of cultured EC. The specific expression of CD44 on activated and tumor EC prompted us to study the usefulness of CD44 as an endothelial target for therapy with immunotoxins. In vitro experiments showed that EC are efficiently killed after targeting immunotoxin to CD44.

scholarly journals Role of Vitamin D Receptor in the Antiproliferative Effects of Calcitriol in Tumor-Derived Endothelial Cells and Tumor Angiogenesis In vivo

2009 ◽  
Vol 69 (3) ◽  
pp. 967-975 ◽  
Author(s):  
Ivy Chung ◽  
Guangzhou Han ◽  
Mukund Seshadri ◽  
Bryan M. Gillard ◽  
Wei-dong Yu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Endothelial Cells ◽  
Vitamin D Receptor ◽  
Tumor Angiogenesis ◽  
Antiproliferative Effects

Dual role of EZH2 on megakaryocyte differentiation

Blood ◽  
2021 ◽  
Author(s):  
Stefania Mazzi ◽  
Philippe Dessen ◽  
Mathieu Vieira ◽  
Virginie Dufour ◽  
Marie Cambot ◽  
...  
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Transcriptome Profiling ◽  
Loss Of Function ◽  
Expression Of Genes ◽  
Key Factor ◽  
Dna Replication And Repair ◽  
Proplatelet Formation

EZH2, the enzymatic component of PRC2, has been identified as a key factor in hematopoiesis. EZH2 loss of function mutations have been found in myeloproliferative neoplasms, more particularly in myelofibrosis, but the precise function of EZH2 in megakaryopoiesis is not fully delineated. Here, we show that EZH2 inhibition by small molecules and shRNA induces MK commitment by accelerating lineage marker acquisition without change in proliferation. Later in differentiation, EZH2 inhibition blocks proliferation, polyploidization and decreases proplatelet formation. EZH2 inhibitors similarly reduce MK polyploidization and proplatelet formation in vitro and platelet level in vivo in a JAK2V617F background. In transcriptome profiling, the defect in proplatelet formation was associated with an aberrant actin cytoskeleton regulation pathway, whereas polyploidization was associated with an inhibition of expression of genes involved in DNA replication and repair, and an upregulation of CDK inhibitors, more particularly CDKN1A and CDKN2D. The knockdown of CDKN1A and at a lesser extend of CDKN2D could partially rescue the percentage of polyploid MKs. Moreover, H3K27me3 and EZH2 ChIP assays revealed that only CDKN1A is a direct EZH2 target while CDKN2D expression is not directly regulated by EZH2 suggesting that EZH2 controls MK polyploidization directly through CDKN1A and indirectly through CDKN2D.

MEKK3 is required for endothelium function but is not essential for tumor growth and angiogenesis

2007 ◽  
Vol 293 (4) ◽  
pp. C1404-C1411 ◽  
Author(s):  
Yong Deng ◽  
Jianhua Yang ◽  
Marya McCarty ◽  
Bing Su
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Critical Role ◽  
Embryonic Stem ◽  
Angiogenic Factor ◽  
Endothelial Cell Proliferation ◽  
Wild Type

Mitogen-activated protein kinase kinase kinase 3 (MEKK3) plays an essential role in embryonic angiogenesis, but its role in tumor growth and angiogenesis is unknown. In this study, we further investigated the role of MEKK3 in embryonic angiogenesis, tumor angiogenesis, and angiogenic factor production. We found that endothelial cells from Mekk3-deficient embryos showed defects in cell proliferation, apoptosis, and interactions with myocardium in the heart. We also found that MEKK3 is required for angiopoietin-1 (Ang1)-induced p38 and ERK5 activation. To study the role of MEKK3 in tumor growth and angiogenesis, we established both wild-type and Mekk3-deficient tumor-like embryonic stem cell lines and transplanted them subcutaneously into nude mice to assess their ability to grow and induce tumor angiogenesis. Mekk3-deficient tumors developed and grew similarly as control Mekk3 wild-type tumors and were also capable of inducing tumor angiogenesis. In addition, we found no differences in the production of VEGF in Mekk3-deficient tumors or embryos. Taken together, our results suggest that MEKK3 plays a critical role in Ang1/Tie2 signaling to control endothelial cell proliferation and survival and is required for endothelial cells to interact with the myocardium during early embryonic development. However, MEKK3 is not essential for tumor growth and angiogenesis.

scholarly journals CD44 Is Involved in Tumor Angiogenesis; an Activation Antigen on Human Endothelial Cells

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1150-1159 ◽  
Author(s):  
Arjan W. Griffioen ◽  
Marieke J.H. Coenen ◽  
Cora A. Damen ◽  
Sandra M.M. Hellwig ◽  
David H.J. van Weering ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Tumor Angiogenesis ◽  
Umbilical Vein ◽  
Human Endothelial Cells ◽  
Specific Expression ◽  
Cd44 Expression ◽  
Activation Antigen

CD44 is described to be an activation molecule in a number of different cell types. We investigated the role of CD44 on human endothelial cells (EC) and in tumor angiogenesis. Using flow cytometry we showed that EC from the vasculature of human solid tumors display an enhanced expression of CD44 as compared to EC from normal tissue. This finding was confirmed by immunohistochemical studies on frozen tissue sections. Because tumors are dependent on angiogenesis, the role of angiogenic stimuli in the enhanced CD44 expression was investigated. We found that basic fibroblast growth factor (bFGF ) and vascular endothelial growth factor were able to efficiently upregulate CD44 expression on cultured human EC. The upregulation reached maximal levels after treatment for 3 days with 10 ng/mL bFGF. The physiological impact of this upregulation was shown by the enhanced binding of EC to hyaluronate after pretreatment with bFGF. In a next set of studies that were designed to unravel the regulation of CD44 expression on EC we concluded that CD44 is an activation antigen on human EC since (1) human umbilical vein derived endothelial cells, which in vivo do not express CD44, begin to express CD44 when plated and cultured, (2) CD44 expression is enhanced after subculture of confluent cultures, (3) CD44 is predominantly expressed on the BrdU incorporating subset of cultured EC. The specific expression of CD44 on activated and tumor EC prompted us to study the usefulness of CD44 as an endothelial target for therapy with immunotoxins. In vitro experiments showed that EC are efficiently killed after targeting immunotoxin to CD44.

scholarly journals Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyunjin Yoo ◽  
Young Jae Lee ◽  
Chanhyeok Park ◽  
Dabin Son ◽  
Dong Yoon Choi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymphatic Vessels ◽  
Genetic Studies ◽  
Hematopoietic Stem ◽  
Genetic Ablation ◽  
Multiple Organs ◽  
Expression Of Genes ◽  
Lymphatic Development ◽  
And Function

AbstractProper functioning of the lymphatic system is required for normal immune responses, fluid balance, and lipid reabsorption. Multiple regulatory mechanisms are employed to ensure the correct formation and function of lymphatic vessels; however, the epigenetic modulators and mechanisms involved in this process are poorly understood. Here, we assess the regulatory role of mouse Dot1l, a histone H3 lysine (K) 79 (H3K79) methyltransferase, in lymphatic formation. Genetic ablation of Dot1l in Tie2(+) endothelial cells (ECs), but not in Lyve1(+) or Prox1(+) lymphatic endothelial cells (LECs) or Vav1(+) definitive hematopoietic stem cells, leads to catastrophic lymphatic anomalies, including skin edema, blood–lymphatic mixing, and underdeveloped lymphatic valves and vessels in multiple organs. Remarkably, targeted Dot1l loss in Tie2(+) ECs leads to fully penetrant lymphatic aplasia, whereas Dot1l overexpression in the same cells results in partially hyperplastic lymphatics in the mesentery. Genetic studies reveal that Dot1l functions in c-Kit(+) hemogenic ECs during mesenteric lymphatic formation. Mechanistically, inactivation of Dot1l causes a reduction of both H3K79me2 levels and the expression of genes important for LEC development and function. Thus, our study establishes that Dot1l-mediated epigenetic priming and transcriptional regulation in LEC progenitors safeguard the proper lymphatic development and functioning of lymphatic vessels.

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