Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecules of the cadherin and integrin families involved in cell-cell and cell-matrix adhesion have been implicated in epithelial differentiation, carcinogenesis and metastasis. Having observed that a colon cancer cell line bound avidly to collagen type I, inducing integrin-triggered glandular differentiation, we investigated the regulation of integrin function in these cells. We modified a mammalian expression cloning system that used monoclonal antibody selection to clone cell surface molecules. Using attachment to collagen type I to select for adhesive phenotype, we isolated a complementary DNA clone that increases cell adhesion to components of the extracellular matrix. The corresponding gene (cell adhesion regulator, CAR) is located on the long arm of chromosome 16 (16q) and encodes a protein of 142 amino acids, which has an N-terminal myristoylation motif and a consensus tyrosine-kinase phosphorylation site at the C terminus. Removal of this tyrosine residue abolishes enhancement of cell-matrix adhesion. This gene may encode an adhesion signal transduction molecule that functions in the suppression of tumour invasion.
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PMID:Cloning and characterization of a gene that regulates cell adhesion. 842 14

Vascular endothelial-cadherin (VE-cadherin), a calcium-dependent homotypic adhesion molecule, contributes to endothelial assembly and VEGF-mediated survival during angiogenesis. In human term placentas, villous vessels and extravillous cytotrophoblasts express VE-cadherin. Therefore, the purpose of this study was to examine if VEGF modulated placental development by increasing the expression of VE-cadherin in rat placentas. Placental tissues from rats on gestation days 14 (G14), 18 (G18) and 21 (G21) were used. Western blot analysis and immunohistochemistry were performed to detect the protein abundance and the distribution of VE-cadherin. A nitric oxide analyzer was used to measure the released nitric oxide (NO) from placental explant culture. With the progression of pregnancy, the abundance of VE-cadherin and the intensity of the immunoreactive staining for VE-cadherin in endovascular trophoblasts and labyrinth trophoblasts were decreased. In explant culture, VEGF (0.01-1.0 ng/ml) increased the protein abundance of VE-cadherin. SNP (an NO donor) or L-arginine (substrate for eNOS) induced the expression of VE-cadherin with the increase of NO production. L-NAME (a NOS inhibitor) reduced the VEGF-increased expression and L-arginine reversed the inhibitory effect of L-NAME. In conclusion, VEGF plays an important role in placental development by the induction of VE-cadherin in trophoblasts, which, in part, maintains the survival of labyrinth trophoblast in rat placentas.
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PMID:Induction of VE-cadherin in rat placental trophoblasts by VEGF through a NO-dependent pathway. 1570 25

Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis.
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PMID:Nitric Oxide Increases Arterial Endotheial Permeability through Mediating VE-Cadherin Expression during Arteriogenesis. 2613 49

VEGF is known to cause vascular leak, its detailed mechanisms in vivo remain unclear. Here, we investigated the mechanisms underlying VEGF-induced vascular hyper-permeability focusing on two major regulators of vascular permeability: blood flow and endothelial barrier function. Administration of VEGF caused vascular hyper-permeability and tissue swelling in mouse ears, which were abolished by VEGF receptor-2 blockade. Intravital imaging showed that VEGF dilated ear arteries but not veins, and laser Doppler velocimetry showed that VEGF quickly increased tissue blood flow along with arterial dilation. Whole-mount immunostaining showed that VEGF phosphorylated endothelial nitric oxide synthase (eNOS) at residue Ser1177 and disrupted the alignment of vascular endothelial-cadherin (VE-cadherin) around the endothelial cell borders in mouse ear skin, indicating endothelial nitric oxide (NO) production and barrier disruption. Administration of the nitric oxide synthesis inhibitor, L-NAME, as well as the vasoconstrictor phenylephrine, abolished all VEGF-induced responses, including blood flow increase, dye leakage, and tissue swelling. However, these two treatments did not alter the intracellular localization of VE-cadherin-induced by VEGF. These observations underscore the importance of vascular dilation and, subsequent increase in blood flow, as well as, endothelial barrier disruption in the mechanisms of VEGF-induced vascular hyper-permeability.
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PMID:VEGF-induced blood flow increase causes vascular hyper-permeability in vivo. 2616 62