Perlecan Regulates Oct-i Gene Expression in Vascular Smooth Muscle Cells
Perlecan Regulates Oct-i Gene Expression in Vascular Smooth Muscle Cells
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血管平滑肌细胞（SMC）在成熟血管中非常静止，并且在基因表达中表现出显著的表型依赖性多样性，这可能反映了这些细胞在各种正常和病理条件下的生长反应性。在这份报告中，我们描述的表达模式的Oct-i，一个家庭的成员参与细胞生长过程中的转录因子，在培养和在体内SMC。Oct-I mRNA在体内SMC的收缩状态中检测不到;在体内SMC-细胞外基质相互作用破坏后诱导;并且由培养的SMC组成型表达。Oct-I转录抑制时，培养的SMCs平板上Engelbreth-Holm-Swarm肿瘤衍生的基底膜（EHS-BM），但SMC-EHS-BM接触中断后迅速诱导;再表达在转录水平调节。为了鉴定参与Oct-i mRNA表达的主动抑制的EHS-BM组分，将SMC铺在层粘连蛋白、IV型胶原、纤连蛋白或串珠素基质上。当SMC在由层粘连蛋白、IV型胶原蛋白或纤连蛋白组成的基质上培养时，可以容易地检测到Oct-i mRNA水平，但当SMC在串珠状基质上培养时，Oct-i mRNA水平被抑制。最后，EHS-BM的Oct-I抑制活性对肝素酶消化敏感，但对软骨素酶ABC或透明质酸酶消化不敏感，表明串珠素的硫酸乙酰肝素侧链在负调节Oct-I转录物的表达中起生物学重要作用。
Vascular smooth muscle cells (SMCs) are very quiescent in the mature vessel and exhibit a remarkable phenotype-dependent diversity in gene expression that may reflect the growth responsiveness of these cells under a variety of normal and pathological conditions. In this report, we describe the expression pattern of Oct-i, a member of a family of transcription factors involved in cell growth processes, in cultured and in in vivo SMCs. Oct-I mRNA was undetectable in the contractile-state in vivo SMCs; was induced upon disruption of in vivo SMC-extracellular matrix interactions; and was constitutively expressed by cultured SMCs. Oct-I transcripts were repressed when cultured SMCs were plated on Engelbreth-Holm-Swarm tumor-derived basement membranes (EHS-BM) but were rapidly induced after disruption of SMC-EHS-BM contacts; reexpression was regulated at the transcriptional level. To identify the EHS-BM component involved in the active repression of Oct-i mRNA expression, SMCs were plated on laminin, type IV collagen, fibronectin, or perlecan matrices. Oct-i mRNA levels were readily detectable when SMCs were cultured on matrices composed of laminin, type IV collagen, or fibronectin but were repressed when SMCs were cultured on perlecan matrices. Finally, the Oct-l-suppressing activity of EHS-BM was sensitive to heparinase digestion but not to chondroitinase ABC or hyaluronidase digestion, suggesting that the heparan sulfate side chains of perlecan play a biologically important role in negatively regulating the expression of Oct-i transcripts.