Clec14a is specifically expressed in endothelial cells and mediates cell to cell adhesion

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 01/2011; 404(1):103-8. DOI: 10.1016/j.bbrc.2010.11.075
Source: PubMed

ABSTRACT Clec14a is a member of the thrombomodulin (TM) family, but its function has not yet been determined. Here, we report that Clec14a is a plasma membrane protein of endothelial cells (ECs) expressed specifically in the vasculature of mice. Deletion mutant analysis revealed that Clec14a mediates cell-cell adhesion through its C-type lectin-like domain. Knockdown of Clec14a in ECs suppressed cell migratory activity and filopodial protrusion, and delayed formation of tube-like structures. These findings demonstrate that Clec14a is a novel EC-specific protein that appears to play a role in cell-cell adhesion and angiogenesis.

11 Reads
  • Source
    • "The slides were blocked in 3% BSA for 60 minutes. As the primary antibodies, rabbit anti-ET-1 polyclonal antibody (1∶250, Peninsula Laboratories) and Isolectin IB4 Alexa Fluor 488 dye conjugate (1∶200, Invitrogen) were applied to the sections overnight at 4°C [16], [17]. After excess antibody was washed out with PBS, a species-matched Alexa 546-labeled secondary antibody (Invitrogen) was added. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Endothelin (ET)-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF)-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF)-α and connective tissue growth factor (CTGF) were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.
    PLoS ONE 05/2014; 9(5):e97972. DOI:10.1371/journal.pone.0097972 · 3.23 Impact Factor
  • Source
    • "Clec14a encodes an endothelial cell-specific protein that plays a role in cell-cell adhesion. Knockdown of Clec14a with siRNA suppressed cell migratory activity in vitro (32). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Carotid atherosclerosis is the primary cause of ischemic stroke. To identify genetic factors contributing to carotid atherosclerosis, we performed quantitative trait locus (QTL) analysis using female mice derived from an intercross between C57BL/6J (B6) and BALB/cJ (BALB) apolipoprotein E (Apoe-/-) mice. 266 F2 mice were started on a Western diet at 6 weeks of age and fed the diet for 12 weeks. Atherosclerotic lesions in the left carotid bifurcation and plasma lipid levels were measured. 130 microsatellite markers across the entire genome were genotyped. Three significant QTLs, Cath1 on chromosome (Chr) 12, Cath2 on Chr5, and Cath3 on Chr13, and four suggestive QTLs on Chr6, Chr9, Chr17, and Chr18 were identified for carotid lesions. The Chr6 locus replicated a suggestive QTL and was named Cath4. Six QTLs for HDL, three QTLs for non-HDL cholesterol, and three QTLs for triglyceride were found. Of these, a significant QTL for non-HDL on Chr1 at 60.3 cM, named Nhdl13, and a suggestive QTL for HDL on ChrX were new. A significant locus for HDL (Hdlq5) was overlapping with a suggestive locus for carotid lesions on Chr9. A significant correlation between carotid lesion sizes and HDL cholesterol levels was observed in the F2 population (R=-0.153, P=0.0133). We have identified several new QTLs for carotid atherosclerosis and the locus on Chr9 may exert effect through interactions with HDL.
    Physiological Genomics 03/2013; 45(8). DOI:10.1152/physiolgenomics.00099.2012 · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tumor endothelial markers (TEMs) that are highly expressed in human tumor vasculature compared with vasculature in normal tissue hold clear therapeutic potential. We report that the C-type lectin CLEC14A is a novel TEM. Immunohistochemical and immunofluorescence staining of tissue arrays has shown that CLEC14A is strongly expressed in tumor vasculature when compared with vessels in normal tissue. CLEC14A overexpression in tumor vessels was seen in a wide range of solid tumor types. Functional studies showed that CLEC14A induces filopodia and facilitates endothelial migration, tube formation and vascular development in zebrafish that is, CLEC14A regulates pro-angiogenic phenotypes. CLEC14A antisera inhibited cell migration and tube formation, suggesting that anti-CLEC14A antibodies may have anti-angiogenic activity. Finally, in endothelial cultures, expression of CLEC14A increased at low shear stress, and we hypothesize that low shear stress due to poor blood flow in the disorganized tumor vasculature induces expression of CLEC14A on tumor vessels and pro-angiogenic phenotypes.
    Oncogene 06/2011; 31(3):293-305. DOI:10.1038/onc.2011.233 · 8.46 Impact Factor
Show more