Disease relevance of Nid2

• Nidogen-2 deficiency does not lead to hemorrhages in mice as one may have expected [1].

High impact information on Nid2

• Fragments alpha2LG1-3 and alpha2LG4-5 also bound to fibulin-1, fibulin-2 and nidogen-2 with Kd = 13-150 nM [2].
• In mammals two nidogen proteins, nidogen-1 and nidogen-2, have been discovered [1].
• Our results show that nidogen-2 is not essential for basement membrane formation or maintenance [1].
• This occurs by either redistribution from other extracellular matrices or unmasking of nidogen 2 epitopes, as its production does not appear to be upregulated [3].
• In embryos, nidogen-2 mRNA was produced by mesenchyme at sites of epithelial-mesenchymal interactions, but the protein was deposited on epithelial basement membranes, as previously shown for nidogen-1 [4].

Biological context of Nid2

• In addition, the tissue distribution of entactin-2 mRNA resembled that of entactin [5].
• Although deduction of the amino acid sequence of entactin-2 revealed only 27.4% homology to entactin, many structural similarities were seen between both proteins [5].
• The data support the nidogen-2 compensation hypothesis to explain the limited phenotype observed following elimination of the nidogen-1 gene [6].
• Most remarkably, expression of the entactin-2 homolog entactin-1 dramatically declined in myogenesis, suggesting different functions of the two entactins in this process [7].
• Nidogen-1 and nidogen-2 are found in basement membranes during human embryonic development [8].

Anatomical context of Nid2

• Both nidogen-1 and nidogen-2 mRNAs are found not only in mesenchymal cells of embryonic tissues, but also in all epithelial and endothelial cells in adult mouse kidney [9].
• Treatment of C2C12 myoblasts with actinomycin D in parallel to the induction of differentiation could demonstrate that this is due to enhanced transcription of the entactin-2 gene [7].

Associations of Nid2 with chemical compounds

• The rod-like domain of entactin-2, containing the RGD integrin recognition sequence, fused to glutathione-S transferase (GST), revealed a cell surface-binding activity similar to that of entactin [5].
• Furthermore, treatment with the translation inhibitor cycloheximide could show that entactin-2 is a primary response gene [7].

Other interactions of Nid2

• We localized expression of nidogen-1 and nidogen-2 on prenatal days 12, 14, and 16 in the developing mouse liver using in situ hybridization at the light and electron microscopic level and light microscopic immunohistochemistry [10].
• The mRNA of laminin alpha1, laminin beta1, collagen type IV, nidogen-2 and perlecan were expressed in the ectoderm-derived mesoderm, in the endoderm as well as in the ectoderm [11].
• As p38 MAP kinase is an important regulator of myogenic differentiation, we also analyzed the possibility that entactin-2 might be a target of this pathway [7].

Analytical, diagnostic and therapeutic context of Nid2

• We have now localized nidogen-1 and nidogen-2, as well as their corresponding mRNAs, at the light and electron microscopic levels in adult mouse kidney, by in situ hybridization and immunogold histochemistry, as well as carrying out double labeling with laminin-1 [9].
• Furthermore, decreased expression of the entactin-2 gene after treatment of the cells with ent-2-specific siRNA preparation led to reduced expression of the cell cycle inhibitor p21 [7].

References