Brill Shlomo, Zvibel Isabel, Halpern Zamir, Oren Ran
Liver Research Group, Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel.
Eur J Cell Biol. 2002 Jan;81(1):43-50. doi: 10.1078/0171-9335-00200.
We explored the effect of extracellular matrix (ECM) produced by fetal and adult hepatocytes on tissue-specific gene expression and proliferation of fetal and adult hepatocytes. Adult hepatocytes ECM strongly induced expression of both albumin and HNF-4 in adult hepatocytes. In contrast, fibroblast ECM reduced the expression of mRNAs for albumin and alpha-fetoprotein in fetal hepatocytes. Adult hepatocytes ECM also increased the activity of liver-specific enzymes of adult hepatocytes (DPP IV and glucose-6-phosphatase) in both fetal and adult hepatocytes, while fetal hepatocyte-derived ECM increased activity of the fetal hepatocyte enzyme GGT in fetal hepatocytes. Fibroblast ECM was inhibitory for the activity of all enzymes assayed. Removal of heparin chains from the various matrices by pretreatment of the ECM with heparinase resulted in reduction of glucose-6-phosphatase and DPP IV in adult hepatocytes. Removal of chondroitin sulfate chains from fetal hepatocyte-derived ECM resulted in loss of induction of GGT in the fetal cells. Fetal hepatocytes proliferated best on adult hepatocyte-derived ECM. Adult hepatocytes showed only modest proliferation on both fetal and adult hepatocytes ECM and their growth was inhibited by fibroblast ECM. In conclusion, adult hepatocyte ECM better supports the expression of adult genes, whereas fetal hepatocyte ECM induced expression of fetal genes. Fibroblast derived-ECM was inhibitory for both proliferation and tissue-specific gene expression in fetal and adult hepatocytes. The data support a role for heparan sulfate being the active element in adult ECM, and chondroitin sulfate being the active element in fetal ECM.
我们探究了胎儿和成人肝细胞产生的细胞外基质（ECM）对胎儿和成人肝细胞组织特异性基因表达及增殖的影响。成人肝细胞ECM强烈诱导成人肝细胞中白蛋白和肝细胞核因子4（HNF-4）的表达。相比之下，成纤维细胞ECM降低了胎儿肝细胞中白蛋白和甲胎蛋白mRNA的表达。成人肝细胞ECM还增加了胎儿和成人肝细胞中成人肝细胞特异性酶（二肽基肽酶IV和葡萄糖-6-磷酸酶）的活性，而胎儿肝细胞来源的ECM增加了胎儿肝细胞中胎儿肝细胞酶γ-谷氨酰转肽酶（GGT）的活性。成纤维细胞ECM对所有检测的酶活性均有抑制作用。用肝素酶预处理ECM以去除各种基质中的肝素链，导致成人肝细胞中葡萄糖-6-磷酸酶和二肽基肽酶IV减少。从胎儿肝细胞来源的ECM中去除硫酸软骨素链导致胎儿细胞中GGT诱导作用丧失。胎儿肝细胞在成人肝细胞来源的ECM上增殖最佳。成人肝细胞在胎儿和成人肝细胞ECM上仅适度增殖，其生长受到成纤维细胞ECM的抑制。总之，成人肝细胞ECM能更好地支持成人基因的表达，而胎儿肝细胞ECM诱导胎儿基因的表达。成纤维细胞来源的ECM对胎儿和成人肝细胞的增殖及组织特异性基因表达均有抑制作用。这些数据支持硫酸乙酰肝素是成人ECM中的活性成分，硫酸软骨素是胎儿ECM中的活性成分这一观点。
