THE EFFECT OF EXTRACELLULAR-MATRIX PROTEINS ON PORCINE SMOOTH-MUSCLE CELL INSULIN-LIKE-GROWTH-FACTOR (IGF) BINDING PROTEIN-5 SYNTHESIS AND RESPONSIVENESS TO IGF-I

The aim of this study was to determine if cultured porcine vascular sm ooth muscle cells (pSMCs) that had been maintained on different extrac ellular matrix proteins had an alteration in their expression of insul in-like growth factor binding protein-5 (IGFBP-5) and their responsive ness to insulin like growth factor-I (IGF-I). When pSMCs were plated o n fibronectin, they synthesized 6.0 +/- 1.2-fold more IGFBP-5 than did cells maintained on laminin and type TV collagen. IGF-I increased IGF BP-5 gene expression 3-fold in the cells plated on fibronectin. The ad dition of an RGD peptide and echistatin to pSMC cultures that had been plated on fibronectin inhibited IGFBP-5 mRNA expression. The addition of an antibody against alpha(2) beta(1) integrin partially reversed t he inhibitory effects of laminin and type IV collagen on IGFBP-5 expre ssion. Cells maintained on fibronectin had a 5.0 +/- 1.1-fold greater DNA synthesis response to IGF-I compared with those maintained on lami nin/type TV collagen, and echistatin significantly inhibited the DNA s ynthesis response of the fibronectin-maintained cells to IGF-I. The an ti-alpha(2) beta(1) antibody partially reversed the inhibitory effect of laminin and type TV collagen on IGF-I stimulated DNA synthesis. The addition of IGFBP-5 to cultures plated on laminin and type TV collage n significantly increased their response to IGF-I. Atherosclerotic pla ques from pig aorta contained abundant fibronectin and had increased I GFBP-5 mRNA (4.5 +/- 1.5-fold) compared with tissue from the normal ve ssel wall that had a low fibronectin content. These results indicate t hat fibronectin, laminin, and type TV collagen have major effects on I GFBP-5 expression and on IG;F-I-stimulated pSMC responses and that the se effects are mediated by their respective integrins.