Disease relevance of Nid1

• Radiolabeled probes prepared by nicktranslation of p lambda 1E were used to monitor the steady-state levels of entactin mRNA in F9 embryonal carcinoma cells that were induced to differentiate by exposure to retinoic acid and dibutyryl cyclic AMP [1].
• Western blots showed a marked increase in the urinary 55 kDa nidogen fragment as early as the first day following ischemia-reperfusion injury and continuing for six days [2].
• Northern blot analysis of total RNA extracted from normal and damaged liver tissue showed a distinct increase of entactin specific transcripts during development of fibrosis [3].
• In PHN, no differences in type IV collagen, entactin, laminin, fibronectin, or anionic charge content of GBM were found compared with control, even though profound albuminuria was evident from Day 5 through 84 [4].
• Induction of rat yolk sac carcinomas with consistent pattern of laminin, entactin, and type IV collagen biosynthesis [5].

High impact information on Nid1

• Protein A-gold immunocytochemistry was applied in combination with morphometrical approaches to reveal the alpha 1(IV), alpha 2(IV), and alpha 3(IV) chains of type IV collagen as well as entactin on renal basement membranes, particularly on the glomerular one, during maturation [6].
• In the glomerulus at the capillary loop stage, both the epithelial and endothelial cell basement membranes were labeled for the alpha 1(IV) and alpha 2(IV) chains of type IV collagen and entactin [6].
• The Arg-Gly-Asp cell recognition sequence is present in one of the EGF-type repeats, and a synthetic peptide from the putative cell-binding site of entactin was found to promote the attachment of mouse mammary tumor cells [7].
• The complete amino acid sequence of mouse entactin has been derived from sequencing of cDNA clones [7].
• The major constituents of this reconstituted matrix are collagen type IV, laminin, heparan sulfate proteoglycan, entactin, and nidogen [8].

Chemical compound and disease context of Nid1

• Taken together, these in vivo data strongly support the notion that the nidogen breakdown products are the result of partial degradation of tubular basement membrane by meprin A following renal tubular ischemia-reperfusion injury [2].

Biological context of Nid1

• The entactin gene is expressed early in mouse embryogenesis [1].
• Two cDNA clones complementary to rat entactin mRNA were isolated by antibody screening of an oligo(dT)-primed cDNA library constructed in the lambda gt11 expression vector [1].
• The cDNA insert, 1328 base pairs long, was sequenced and found to contain an open reading frame of 729 base pairs that coded for 243 amino acids at the carboxyl terminus of entactin [1].
• Perturbation experiments using monoclonal antibodies directed against entactin-1 (nidogen-1) were performed with peritubular cells and Sertoli cells, respectively, and demonstrated loss of cell adhesion of the peritubular cells, while the Sertoli cells remained adherent [9].
• Treatment with N-glycanase reduces the molecular mass of entactin and eliminates 9H6 binding, suggesting that the 9H6 epitope at synapses is dependent on glycosylation [10].

Anatomical context of Nid1

• Entactin is a widely distributed basement membrane sulfated glycoprotein of approximately equal to 150 kDa [1].
• This mRNA was translated in rabbit reticulocyte lysates to yield a polypeptide of 143 kDa that was precipitated with anti-entactin antiserum [1].
• No entactin-1 (nidogen-1) was detected in the Sertoli cells by Western blotting [9].
• Mesenchymal entactin-1 (nidogen-1) is required for adhesion of peritubular cells of the rat testis in vitro [9].
• The uterine luminal epithelium, the glandular epithelium, and the myometrial smooth muscle cells stained strongly from gestational days 1-8 with both nidogen antibodies [11].

Associations of Nid1 with chemical compounds

• We have purified the factor responsible for this effect from medium conditioned by bovine corneal endothelial cells, and have shown that it is composed of the glycoprotein laminin and two associated laminin-binding molecules: a sulfated protein known as entactin, and a large heparan sulfate proteoglycan [12].
• The RGD (RGDS-NH2) sequence, found in the cell binding domain of the integrin family of cell adhesion molecules as well as in the A chain of laminin and in entactin, effectively inhibited Sertoli cell cord formation at a concentration of 1.0 mg/ml but was unable to prevent Sertoli cell attachment at concentrations as high as 2.0 mg/ml [13].
• Laminin is a cross-shaped glycoprotein whose inner cross-region binds to the glycoprotein entactin (nidogen) forming a stable complex extractable from basement membrane matrices with chelating agents [14].
• Meprin A also degraded purified nidogen into similar breakdown products [2].
• Slot blot analysis of poly-A RNA demonstrated a significant (P < 0.01) increase in the level of entactin messenger RNA (mRNA) by 140% (P < 0.01) and a 50% reduction of type IV collagen alpha1 chain mRNA after thyroid hormone treatment [15].

Regulatory relationships of Nid1

• The entactin mRNA throughout the alveolar walls of neonatal animals was not limited to cells that expressed surfactant-associated protein C mRNA, a marker of alveolar type II cells [16].

Other interactions of Nid1

• At day 6, nidogen-2 immunoreactivity was higher in the primary decidual cells close to the embryo than nidogen-1, and during development of the decidual tissue both nidogens appeared in the endometrial stromal cells [11].
• Furthermore, we observed that the protein levels of laminin, entactin, and fibronectin in an extracellular matrix (ECM)-enriched preparation decreased shortly after partial hepatectomy, and were restored later [17].
• Therefore, we concluded that the alveolar epithelial cells synthesize laminin-1, entactin, type IV collagen, and perlecan, but that they also needed to assemble exogenous laminin-1 into the basement membrane to complete its formation in vitro [18].
• One contains alpha'mbeta1gamma1, co-precipitates with entactin and is assembled into the fibrillar extracellular matrix [19].
• On the opposite, cocultures enriched with PROb cells made more entactin and SPARC and approximately equal amounts of tenascin [20].

Analytical, diagnostic and therapeutic context of Nid1

• Even though the entactin-1 (nidogen-1) gene is transcribed in peritubular cells, Sertoli cells, and in direct cocultures, the mRNA is translated only by the peritubular cells [9].
• Metabolic labeling of PYS cells in organ culture clearly demonstrated the presence of laminin, type IV procollagen, and entactin both in the medium and in tissues, but fibronectin was absent [21].
• N-terminal sequence analysis also indicates that the 9H6 antigen is related to entactin [10].
• Immunoprecipitation of radiolabeled proteins from media of 5-day-old Ito cell primary cultures showed that these cells secreted high levels of the major basement membrane components, ie, collagen IV, laminin, and entactin/nidogen [22].
• In situ hybridization indicated that >60% of the alveolar epithelial cells expressed entactin mRNA with increasing time in culture [16].

References