Disease relevance of NID1

• In primary tumors, we detected NID1 promoter methylation in 67% of colon cancer samples and in 90% of gastric cancers [1].
• Loss of nidogen expression may favor invasion and metastasis of cancer cells by loosening cell interaction with basal membrane and by weakening the strength of the basement membrane itself, first barrier from the connective vascularized matrix [1].
• Nidogen 1 and 2 gene promoters are aberrantly methylated in human gastrointestinal cancer [1].
• However, the human choriocarcinoma cell line JEG-3, which expressed laminin genes, did not contain detectable levels of nidogen mRNAs [2].
• Quantitation of the relative nidogen mRNA abundance in HT 1080 fibrosarcoma cells indicated that nidogen mRNA levels were approximately the same as those for the laminin B2 chain [2].

Psychiatry related information on NID1

• Our data suggest that nidogen-2 and nidogen-1, as is known for mouse development, could well participate in cell biological functions during human development [3].

High impact information on NID1

• A number of molecules involved in cell adhesion (e.g. fibronectin, laminin, collagens I and IV, thrombospondin, entactin) have now been identified and the consequent roles that they play in the processes of growth, migration, differentiation and tumor spread have been described [4].
• An accumulation of fibronectin, heparan sulfate proteoglycan, laminin-1, and entactin was observed in the GBM of the affected animals [5].
• The leukocyte response integrin (LRI) is a phagocyte integrin which recognizes the basement membrane protein entactin and the synthetic peptide Lys-Gly-Ala-Gly-Asp-Val (KGAGDV) [6].
• When adherent to surface, the LRI ligands entactin and KGAGDV activate the respiratory burst in polymorphonuclear leukocytes (PMN) and monocytes, as do monoclonal antibodies (mAb) directed at either LRI or IAP [6].
• Entactin stimulates neutrophil adhesion and chemotaxis through interactions between its Arg-Gly-Asp (RGD) domain and the leukocyte response integrin [7].

Chemical compound and disease context of NID1

• A large, low-density form of heparan sulfate proteoglycan was isolated from the Engelbreth-Holm-Swarm (EHS) tumor and demonstrated to bind in immobilized-ligand assays to laminin fragment E3, collagen type IV, fibronectin and nidogen [8].
• Nidogen, obtained from the EHS tumor or in recombinant form, binds exclusively to the protein core in a heparin-insensitive manner [8].
• We have previously described decreased immunostaining of nidogen-1/entactin; laminin chains alpha1, alpha5, beta1,gamma1; and epithelial integrin alpha3beta1 in human diabetic retinopathy (DR) corneas [9].
• The authors have investigated the possible significance of nidogen in Hirschsprung's disease, because this glycoprotein is necessary for the formation of ternary complexes with the other basement membrane components, laminin and collagen type IV, and thus may contribute the pathology of the disease [10].

Biological context of NID1

• RESULTS: We show that CpG islands of both NID1 and NID2 genes are aberrantly methylated in human cancer samples and cancer cell lines [1].
• LAR- laminin-nidogen binding was regulated by alternative splicing of a small exon within the LAR-Fn5 so that inclusion of this exon sequence resulted in disruption of the laminin-nidogen-binding activity [11].
• The fibulin-2 binding site of nidogen could be localized to its C-terminal globular domain G3, which also possesses a high-affinity binding site for laminin-1 [12].
• Anti-IAP antibodies inhibit multiple phagocyte functions, including Arg-Gly-Asp (RGD)-initiated activation of phagocytosis, chemotaxis, and respiratory burst; PMN adhesion to entactin; and PMN transendothelial and transepithelial migration at a step subsequent to tight intercellular adhesion [13].
• Comparison of human cDNA sequences with mouse nidogen sequences revealed 84% identity on the nucleotide level and 88% identity with the deduced amino acid sequence [2].

Anatomical context of NID1

• Long cellular processes were observed when HeLa cells were plated on laminin-nidogen, but not when plated on a fibronectin surface [11].
• Using high-resolution light microscopy, we show here that LN-5 is localized in a bi-membranous conduit-like structure, together with other typical basement membrane components including collagen type IV, nidogen and perlecan [14].
• In some DR corneas, epithelial BM was stained discontinuously for laminin-1, entactin/nidogen, and alpha3-alpha4 Type IV collagen, in contrast to non-DR corneas [15].
• Adhesion of cultured human kidney mesangial cells to native entactin: role of integrin receptors [16].
• RESULTS: In LP-skin and mucosa the thickened vessel walls stained strongly for the BM-components type IV collagen, laminin, perlecan, and nidogen (IIF) [17].

Associations of NID1 with chemical compounds

• The laminin-nidogen complex is a ligand for a specific splice isoform of the transmembrane protein tyrosine phosphatase LAR [11].
• A distinct interaction was also observed with nidogen but this was only partially blocked by EDTA [12].
• Urokinase binding to laminin-nidogen. Structural requirements and interactions with heparin [18].
• Thioflavin T fluorometric assay and electron microscopy revealed that entactin significantly inhibited Abeta1-40 (Abeta40) fibril formation at an Abeta40:entactin molar ratio of 50:1 [19].
• The binding of entactin to either the A alpha chain or the B beta chain was divalent cation-independent [20].

Physical interactions of NID1

• Direct binding assays confirmed that u-PA binds to nidogen through a site in the u-PA ATF [18].
• Adhesion assays with inhibitory anti integrin monoclonal antibodies (mab) demonstrated that CHMC use both alpha v beta 3 and a beta 1-containing integrin to bind surfaces coated with native entactin [16].
• Conversely, the presence of entactin inhibited the binding of perlecan, laminin, and fibronectin to beta PPs [21].

Enzymatic interactions of NID1

• Analyzing the Matrigel proteins, we found that MMP-19 preferentially cleaved nidogen-1 [22].

Regulatory relationships of NID1

• Entactin-induced inhibition of human amyloid beta-protein fibril formation in vitro [19].
• Thoracic discharges from NID-1 were more likely to stimulate the myocardium than those from NID-2 (98% vs. 54%, p = 0.0007) [23].
• Activity of MMP-19 inhibits capillary-like formation due to processing of nidogen-1 [22].

Other interactions of NID1

• Indirect immunofluorescent antibody staining revealed high expression of LAR in a punctate pattern, throughout the length of these cellular processes observed on laminin-nidogen [11].
• We propose that the ability of entactin to induce random structure is linked to the inhibition of Abeta fibril formation [19].
• Nonscarred regions showed decreased staining of the epithelial BM for entactin/nidogen, fibronectin, alpha 3-alpha 5 chains of type IV collagen, and chains of laminin-1 [24].
• The extracellular matrix laminin-nidogen complex was identified as a ligand for the LAR-FnIII domain 5 (Fn5) using a series of GST-LAR-FnIII domain fusion proteins and testing them in in vitro ligand-binding assays [11].
• Interactions with some non-collagenous protein ligands were even stronger, with matrilin-2 binding to fibrillin-2, fibronectin and laminin-1-nidogen-1 complexes, with K (D) values in the range of 10(-8)-10(-11) M [25].

Analytical, diagnostic and therapeutic context of NID1

• Circular dichroism spectroscopy data indicated that entactin induced a random coil structure in Abeta40 [19].
• To test the functional promoter activity of the 5'-flanking genomic DNA, two nidogen promoter/CAT reporter gene constructs, with the promoter segment spanning from -864 to -1 and from -534 to -1, respectively, were developed and analyzed in transient transfections of human and mouse cell cultures [26].
• An approximately 100-kb region of genomic DNA encoding the human nidogen gene (NID) including 5' and 3' flanking sequences has been cloned and characterized by restriction mapping and sequencing [27].
• Also, we used flow cytometry and indirect immunofluorescence to detect the presence of integrins that may be involved in human trophoblast-entactin interaction; these methods were used to analyze HTR cells, as well as tissue sections and freshly isolated human trophoblasts from first trimester and term placenta [28].
• Southern blotting of human leukocyte DNA from 23 individuals indicated that nidogen probably is a single-copy gene and shows multiple restriction fragment length polymorphisms when cleaved with Eco RI, Pvu II, Taq I, and Msp I [29].

References