Suppression of nidogen-1 translation by antisense targeting affects the adhesive properties of cultured astrocytes

The multidomain glycoprotein nidogen-l is a common component of basal membr anes. Nidogen-l is produced by the endothelial cells and the mesenchymal ce lls of the developing central nervous system. Recent results give evidence that; nidogen-l may also be secreted by cultured Schwann cells to basement membranes of peripheral nerves. We were interested in ascertaining whether astrocytes, which have the capacity to produce laminin and fibronectin and are an important source of extracellular matrix (ECM) molecule secretion in the brain, might also produce nidogen-l. Immunocytochemistry, in combinati on with polymerase chain reaction and in situ hybridization techniques, rev ealed that astrocytes in culture synthesize nidogen-l. To show the function al significance of the nidogen-l secretion by astrocytes, antisense targeti ng techniques were applied. These experiments showed that nidogen-l may be an essential modulator of astrocytic adhesion to the substrate. The suppres sion of nidogen-l synthesis by the application of antisense oligonucleotide s induced a morphological transition from a flat, polygonal to a round cell and was accompanied by the detachment of the astrocytes from the substrate . Hence, nidogen-l might be an important component of the ECM secreted by a strocytes. The suppression of nidogen-1 synthesis may disturb the aggregati on of ECM molecules to a functional basement membrane and thus reduce the a strocytic adhesion to the substrate. Nidogen-l secretion to basement membra nes by astrocytes may have important functional implications during blood-b rain barrier and scar formation. (C) 1999 Wiley-Liss, Inc.