Ouchi H, Otsu K, Kuzumaki T, Iuchi Y, Ishikawa K
Department of Biochemistry, Yamagata University School of Medicine, Yamagata, 990-9585, Japan.
Arch Biochem Biophys. 1998 Oct 1;358(1):58-62. doi: 10.1006/abbi.1998.0841.
The extracellular matrix plays an important role for maintaining liver functions. We examined the effects of type I collagen and fibronectin on the expression of liver-specific genes in rat primary hepatocytes. When primary culture hepatocytes were overlaid with a type I collagen-gel, the expression of liver-specific genes (tyrosine aminotransferase, aldolase B, and albumin) increased by 4-5 times, compared with not overlaid hepatocytes. In contrast, the expression of non-liver-specific genes (GAPDH and beta-actin) was suppressed under the same conditions. The addition of fibronectin together with type I collagen-gel further enhanced the expression of liver-specific genes by 1.4-1.8 times. The addition of GRGDS peptide instead of fibronectin with the collagen-gel had a similar effect on hepatic gene expression to that of fibronectin. Addition of fibronectin alone exhibited had no effect on gene expression. These results suggest that type I collagen and fibronectin synergistically induce liver-specific genes.
细胞外基质在维持肝脏功能方面发挥着重要作用。我们研究了I型胶原蛋白和纤连蛋白对大鼠原代肝细胞中肝脏特异性基因表达的影响。当原代培养的肝细胞覆盖I型胶原凝胶时,与未覆盖的肝细胞相比,肝脏特异性基因(酪氨酸转氨酶、醛缩酶B和白蛋白)的表达增加了4 - 5倍。相反,在相同条件下,非肝脏特异性基因(甘油醛-3-磷酸脱氢酶和β-肌动蛋白)的表达受到抑制。将纤连蛋白与I型胶原凝胶一起添加可使肝脏特异性基因的表达进一步增强1.4 - 1.8倍。用GRGDS肽代替纤连蛋白与胶原凝胶一起添加对肝脏基因表达的影响与纤连蛋白相似。单独添加纤连蛋白对基因表达没有影响。这些结果表明,I型胶原蛋白和纤连蛋白协同诱导肝脏特异性基因。