Abstract:
:Vascular endothelial (VE) cadherin is a key component of endothelial adherens junctions (AJs) and plays an important role in maintaining vascular integrity. Endocytosis of VE-cadherin regulates junctional strength and a decrease of surface VE-cadherin reduces vascular stability. However, disruption of AJs is also a requirement for vascular sprouting. Identifying novel regulators of endothelial endocytosis could enhance our understanding of angiogenesis. Here, we evaluated the angiogenic potential of (CKLF-like MARVEL transmembrane domain 4) CMTM4 and assessed in which molecular pathway CMTM4 is involved during angiogenesis. Using a 3D vascular assay composed of GFP-labeled HUVECs and dsRED-labeled pericytes, we demonstrated in vitro that siRNA-mediated CMTM4 silencing impairs vascular sprouting. In vivo, CMTM4 silencing by morpholino injection in zebrafish larvae inhibits intersomitic vessel growth. Intracellular staining revealed that CMTM4 colocalizes with Rab4+ and Rab7+ vesicles, both markers of the endocytic trafficking pathway. CMTM4 colocalizes with both membrane-bound and internalized VE-cadherin. Adenovirus-mediated CMTM4 overexpression enhances the endothelial endocytic pathway, in particular the rapid recycling pathway, shown by an increase in early endosomal antigen-1 positive (EEA1+), Rab4+, Rab11+ , and Rab7+ vesicles. CMTM4 overexpression enhances membrane-bound VE-cadherin internalization, whereas CMTM4 knockdown decreases internalization of VE-cadherin. CMTM4 overexpression promotes endothelial barrier function, shown by an increase in recovery of transendothelial electrical resistance (TEER) after thrombin stimulation. We have identified in this study a novel regulatory function for CMTM4 in angiogenesis. CMTM4 plays an important role in the turnover of membrane-bound VE-cadherin at AJs, mediating endothelial barrier function and controlling vascular sprouting.
journal_name
Angiogenesisjournal_title
Angiogenesisauthors
Chrifi I,Louzao-Martinez L,Brandt MM,van Dijk CGM,Bürgisser PE,Zhu C,Kros JM,Verhaar MC,Duncker DJ,Cheng Cdoi
10.1007/s10456-018-9638-1subject
Has Abstractpub_date
2019-02-01 00:00:00pages
75-93issue
1eissn
0969-6970issn
1573-7209pii
10.1007/s10456-018-9638-1journal_volume
22pub_type
杂志文章相关文献
ANGIOGENESIS文献大全abstract::A missense mutation from arginine to tryptophan at residue 849 in the kinase domain of Tie2 (Tie2-R849W) is commonly identified in familial venous malformations. The mechanistic action of Tie2-R849W variant expression on angiogenic cascades including smooth muscle cell recruitment, however, remains elusive. To avoid c...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-012-9313-x
更新日期:2013-01-01 00:00:00
abstract::Anti-angiogenesis is likely to develop into a novel therapeutic approach for patients with solid malignancies. Most current clinical trials evaluate anti-angiogenic drugs aimed primarily against single angiogenesis stimulators. Here, we show that a single solid malignancy, i.e., a human embryonal rhabdomyosarcoma, pro...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1016045012466
更新日期:2001-01-01 00:00:00
abstract::The lymphatic system is intimately linked to tissue fluid homeostasis and immune cell trafficking. These functions are paramount in the establishment and development of an inflammatory response. In the past decade, an increasing number of reports has revealed that marked changes, such as lymphangiogenesis and lymphati...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-014-9416-7
更新日期:2014-04-01 00:00:00
abstract::Vascularization and endothelial phenotype were investigated in embryonic tissues grafted onto chorioallantoic membrane (CAM) by means of immunocytochemistry and electron microscopy. Single grafts of adrenal gland or cerebellum and double grafts of adrenal gland plus cerebellum were performed, using tissues from chick ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1026550510585
更新日期:1999-01-01 00:00:00
abstract::Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-018-9604-y
更新日期:2018-05-01 00:00:00
abstract::Angiogenesis was postulated to be a critical prognostic factor and therapeutic focus for malignancy more than two decades ago. Recent studies indicate quantitative assessments of microvessel count to be an independent prognostic variable for disease-free and overall survival in a wide variety of tumors, and that angio...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/A:1018301031580
更新日期:1997-01-01 00:00:00
abstract::Although monotherapy with angiostatic drugs is still far from effective, there is abundant evidence that angiostatic therapy can improve the efficacy of conventional treatments like radiotherapy. This has instigated numerous efforts to optimize and clinically implement the combination of angiostatic drugs with radiati...
journal_title:Angiogenesis
pub_type: 历史文章,杂志文章,评审
doi:10.1007/s10456-017-9546-9
更新日期:2017-05-01 00:00:00
abstract::Among the key effects of fluid shear stress on vascular endothelial cells is modulation of gene expression. Promoter sequences termed shear stress response elements (SSREs) mediate the responsiveness of endothelial genes to shear stress. While previous studies showed that shear stress responsiveness is mediated by a s...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-009-9143-7
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Angiogenesis plays a pivotal role in neoplastic growth and metastasis formation. Vascular endothelial growth factor A (VEGFA) is a major player in physiological and tumour-induced angiogenesis and numerous human tumours have been show to overexpress VEGFA. Moreover increased VEGFA gene expression has been fo...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-013-9396-z
更新日期:2014-07-01 00:00:00
abstract::Altered RNA processing is an underlying mechanism of amyotrophic lateral sclerosis (ALS). Missense mutations in a number of genes involved in RNA function and metabolisms are associated with ALS. Among these genes is angiogenin (ANG), the fifth member of the vertebrate-specific, secreted ribonuclease superfamily. ANG ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-012-9322-9
更新日期:2013-04-01 00:00:00
abstract::Vascular anomalies can cause significant morbidity and mortality. Advances in diagnosis will be improved if noninvasive biomarkers can be identified, as obtaining a tissue biopsy can worsen the disease and precipitate complications. The goal of this study was to identify biomarkers for vascular anomaly patients to aid...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-016-9537-2
更新日期:2017-02-01 00:00:00
abstract::CM101, an anti-pathoangiogenic polysaccharide derived from group B streptococcus, has been shown to inhibit inflammatory angiogenesis and accelerate wound healing in a mouse model and minimize scarring/gliosis following spinal cord injury. To evaluate the in vivo effects of CM101 on cutaneous wound healing in the pig,...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1016752925761
更新日期:2001-01-01 00:00:00
abstract::During embryonic development, the lymphatic system emerges by transdifferentiation from the cardinal vein. Although lymphatic and blood vasculature share a close molecular and developmental relationship, they display distinct features and functions. However, even after terminal differentiation, transitions between blo...
journal_title:Angiogenesis
pub_type: 临床试验,杂志文章
doi:10.1007/s10456-012-9264-2
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:EPLIN (epithelial protein lost in neoplasm) is a cytoskeletal associated protein involved in the regulation of actin dynamics and subsequently in cell motility. EPLIN expression is frequently reduced in a variety of cancer cells and tissues and this loss may account for increased invasive traits in cancer ce...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-010-9188-7
更新日期:2010-12-01 00:00:00
abstract::Therapeutic over-expression of vascular endothelial growth factor (VEGF) can be used to treat ischemic conditions. However, VEGF can induce either normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo, which limits its clinical usefulness. The goal herein was ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-012-9304-y
更新日期:2013-01-01 00:00:00
abstract::The chicken chorioallantoic membrane (CAM) is a simple, highly vascularized extraembryonic membrane, which performs multiple functions during embryonic development, including but not restricted to gas exchange. Over the last two decades, interest in the CAM as a robust experimental platform to study blood vessels has ...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-014-9440-7
更新日期:2014-10-01 00:00:00
abstract::Using a fibrin-based angiogenesis model, we have established that there is no canonical mechanism used by endothelial cells (ECs) to degrade the surrounding extracellular matrix (ECM), but rather the set of proteases used is dependent on the mural cells providing the angiogenic cues. Mesenchymal stem cells (MSCs) orig...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-010-9194-9
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:The term "intramuscular hemangioma capillary type" (IHCT) refers to a fast-flow vascular lesion that is classified as a tumor, although its phenotype overlaps with arteriovenous malformation (AVM). The purpose of this study was to identify somatic mutations in IHCT. METHODS:Affected tissue specimens were ob...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-019-09678-w
更新日期:2019-11-01 00:00:00
abstract:OBJECTIVE:Dysregulation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a hallmark of human cancer, occurring in a majority of tumors. Activation of this pathway is critical for transformation and also for the angiogenic switch, which is a key step for tumor progression. The objective of this study was...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-009-9154-4
更新日期:2009-01-01 00:00:00
abstract:PURPOSE:There are currently no validated biomarkers predicting bevacizumab treatment outcome or toxicity. We combined biomarker data from six phase III trials of bevacizumab to assess whether genetic variation in vascular endothelial growth factor-A (VEGF-A) pathway or hypertension-related genes are associated with bev...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-014-9424-7
更新日期:2014-07-01 00:00:00
abstract::Human pancreatic tumors often overexpress the angiogenesis-promoting factor Interleukin 8 (IL-8), in part due to overexpression of NF-kappaB, a frequent occurrence in pancreatic adenocarcinoma. In this study, we demonstrate that reducing c-Src kinase activity, through either pharmacologic inhibition or small interferi...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-006-9038-9
更新日期:2006-01-01 00:00:00
abstract::Heparan sulfate (HS), a long linear polysaccharide of alternating disaccharide residues, interacts with a wide variety of proteins, including many angiogenic factors. The involvement of HS in signaling of pro-angiogenic factors (e.g. vascular endothelial growth factor and fibroblast growth factor 2), as well as intera...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-013-9401-6
更新日期:2014-07-01 00:00:00
abstract::Sunitinib is a potent and clinically approved tyrosine kinase inhibitor that can suppress tumour growth by inhibiting angiogenesis. However, conflicting data exist regarding the effects of this drug on the growth of metastases in preclinical models. Here we use 4T1 and RENCA tumour cells, which both form lung metastas...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-012-9291-z
更新日期:2012-12-01 00:00:00
abstract::Targeted ultrasound contrast imaging has the potential to become a reliable molecular imaging tool. A better understanding of the quantitative aspects of molecular ultrasound technology could facilitate the translation of this technique to the clinic for the purposes of assessing vascular pathology and detecting indiv...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-014-9447-0
更新日期:2015-01-01 00:00:00
abstract::De novo synthesis of cytoskeleton-regulatory proteins triggered by the megakaryoblastic leukemia (MKL)/serum response factor (SRF) transcriptional system in response to pro-angiogenic growth factors lies at the heart of endothelial cell (EC) migration (a critical element of angiogenesis) and neovascularization. This s...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-017-9560-y
更新日期:2017-11-01 00:00:00
abstract::Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancre...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1025803600840
更新日期:2003-01-01 00:00:00
abstract::Pericytes are essential mural cells distinguished by their association with small caliber blood vessels and the presence of a basement membrane shared with endothelial cells. Pericyte interaction with the endothelium plays an important role in angiogenesis; however, very few tools are currently available that allow fo...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-017-9570-9
更新日期:2017-11-01 00:00:00
abstract::Receptor tyrosine kinase c-Kit and its ligand stem cell factor (SCF) regulate resident vascular wall cells and recruit circulating progenitors. We tested whether SCF may be induced by oxidized palmitoyl-arachidonoyl-phosphatidylcholine (OxPAPC) known to accumulate in atherosclerotic vessels. Gene expression analysis d...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-017-9590-5
更新日期:2018-05-01 00:00:00
abstract::Ocular angiogenesis is responsible for the majority of irreversible blindness in the developed world [1]. This debilitating complication affects all age groups and characterizes such diverse and widespread diseases as trachoma, retinopathy of prematurity, diabetic retinopathy, neovascular glaucoma and age-related macu...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1009071601454
更新日期:1999-01-01 00:00:00
abstract::The semaphorins and plexins comprise a family of cysteine-rich proteins implicated in control of nerve growth and development and regulation of the immune response. Our group and others have found that Semaphorin 4D (SEMA4D) and its receptor, Plexin-B1, play an important role in tumor-induced angiogenesis, with some n...
journal_title:Angiogenesis
pub_type: 杂志文章,收录出版
doi:10.1007/s10456-012-9268-y
更新日期:2012-09-01 00:00:00