PERLECAN REGULATES OCT-1 GENE-EXPRESSION IN VASCULAR SMOOTH-MUSCLE CELLS

Vascular smooth muscle cells (SMCs) are very quiescent in the mature v essel and exhibit a remarkable phenotype-dependent diversity in gene e xpression that may reflect the growth responsiveness of these cells un der a variety of normal and pathological conditions. In this report, w e describe the expression pattern of Oct-1, a member of a family of tr anscription factors involved in cell growth processes, in cultured and in in vivo SMCs. Oct-1 mRNA was undetectable in the contractile-state in vivo SMCs; was induced upon disruption of in vivo SMC-extracellula r matrix interactions; and was constitutively expressed by cultured SM Cs. Oct-1 transcripts were repressed when cultured SMCs were plated on Engelbreth-Holm-Swarm tumor-derived basement membranes (EHS-BM) but w ere rapidly induced after disruption of SMC-EHS-BM contacts; reexpress ion was regulated at the transcriptional level. To identify the EHS-BM component involved in the active repression of Oct-1 mRNA expression, SMCs were plated on laminin, type IV collagen, fibronectin, or perlec an matrices. Oct-1 mRNA levels were readily detectable when SMCs were cultured on matrices composed of laminin, type IV collagen, or fibrone ctin but were repressed when SMCs were cultured on perlecan matrices. Finally, the Oct-1-suppressing activity of EHS-BM was sensitive to hep arinase digestion but not to chondroitinase ABC or hyaluronidase diges tion, suggesting that the heparan sulfate side chains of perlecan play a biologically important role in negatively regulating the expression of Oct-1 transcripts.