Kimata Takayuki, Nagaki Masahito, Ogiso Tomio, Naiki Takafumi, Kato Tomohiro, Moriwaki Hisataka
First Department of Internal Medicine, Gifu University School of Medicine, Gifu 501-1194, Japan.
Hepatology. 2006 Jul;44(1):140-51. doi: 10.1002/hep.21215.
Cell adhesion to the extracellular matrix (ECM) plays vital roles in both morphogenesis and regulation of gene expression in cells of adult organisms. How intracellular, cytoskeletal, and signaling factors connect and communicate with the ECM is a fundamental question. Using a cDNA microarray analysis, we identified phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) phosphatase mRNA as being up-regulated in hepatocytes cultured on a basement membrane matrix, Engelbreth-Holm-Swarm (EHS) gel, which led to the finding that the PI(4,5)P2 levels of hepatocytes decreased on EHS gel. These changes in hepatocytes on EHS gel were accompanied by promotion of actin depolymerization and differentiated phenotypes of the hepatocytes. Treatment with PI(4,5)P2 or a phospholipase C inhibitor, U73122, resulted in decreased mRNA expressions of albumin and hepatocyte nuclear factor 4 (HNF-4) in hepatocytes. In contrast, actin-disrupting agent gelsolin increased mRNA expressions of albumin and HNF-4. In conclusion, organization of the actin cytoskeleton via PI(4,5)P2 is involved in the regulation of hepatocyte differentiation by the ECM.
细胞与细胞外基质（ECM）的黏附在成体生物细胞的形态发生和基因表达调控中都起着至关重要的作用。细胞内、细胞骨架和信号因子如何与ECM连接并相互作用是一个基本问题。通过cDNA微阵列分析，我们发现磷脂酰肌醇4,5-二磷酸（PI[4,5]P2）磷酸酶mRNA在铺于基底膜基质恩格尔布雷特-霍尔姆-斯旺（EHS）凝胶上培养的肝细胞中上调，这一发现表明肝细胞在EHS凝胶上时PI(4,5)P2水平降低。肝细胞在EHS凝胶上的这些变化伴随着肌动蛋白解聚的促进和肝细胞分化表型的出现。用PI(4,5)P2或磷脂酶C抑制剂U73122处理导致肝细胞中白蛋白和肝细胞核因子4（HNF-4）的mRNA表达降低。相反，破坏肌动蛋白的试剂凝溶胶蛋白增加了白蛋白和HNF-4的mRNA表达。总之，通过PI(4,5)P2对肌动蛋白细胞骨架的组织参与了ECM对肝细胞分化的调控。
