Pleiotrophin/heparin-binding growth-associated molecule as a mitogen of rat hepatocytes and its role in regeneration and development of liver
Pleiotrophin/heparin-binding growth-associated molecule as a mitogen of rat hepatocytes and its role in regeneration and development of liver
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DOI：
10.1016/s0002-9440(10)61167-4
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发表时间：
2002-06-01
影响因子：
6
通讯作者：
Yoshizato, K
中科院分区：
文献类型：
--
作者：
Asahina, K;Sato, H;Yoshizato, K
此前，多效生长因子（PTN）在瑞士3T3细胞分泌的蛋白质中被鉴定为培养的成年大鼠肝细胞的有丝分裂原。本研究表明，当与大鼠肝星状细胞（HSCs）共培养时，大鼠肝细胞的生长得到增强。在共培养中，HSCs表达PTN mRNA并分泌其蛋白质。重组PTN促进了培养肝细胞的生长，这表明HSCs通过PTN的作用刺激肝细胞生长。为了了解PTN在体内肝细胞生长中的生物学作用，我们检测了PTN在大鼠成年肝脏和胚胎肝脏的四种再生模型中的表达。用D - 半乳糖胺（GalN）或乙酰氨基芴处理后再进行部分肝切除，肝脏中PTN mRNA的表达显著上调。HSCs在GalN处理后表达PTN mRNA，并且在肝细胞上发现其蛋白质。PTN受体N - 多配体聚糖的mRNA表达在GalN处理的肝细胞中上调。横隔中的间充质细胞（包围胚胎肝脏，但不是胚胎HSCs）表达PTN mRNA。我们认为，PTN分别由活化的成年HSCs和胚胎间充质细胞分泌，作为成年肝脏和胚胎肝脏实质细胞的有丝分裂原。
Previously pleiotrophin (PTN) was identified among proteins secreted by Swiss 3T3 cells as a mitogen for cultured adult rat hepatocytes. The present study showed that the growth of rat hepatocytes was enhanced when cultured with rat hepatic stellate cells (HSCs). HSCs expressed PTN mRNA and secreted its protein in the co-cultures. Recombinant PTN enhanced the growth of hepatocytes in culture, suggesting that HSCs stimulate the growth of hepatocytes through the action of PTN. To know the biological role of PTN in the growth of hepatocytes in vivo, we examined the expression of PTN in four regeneration models of adult liver and embryonic liver of rat. The expression of PTN mRNA in the liver was markedly up-regulated by the treatment with D-galactosamine (GalN) or with acetylaminofluorene followed by partial hepatectomy. HSCs expressed PTN mRNA in response to GalN treatment and its protein was found on hepatocytes. The mRNA expression of N-syndecan, a PTN receptor, was up-regulated in GalN-treated hepatocytes. The mesenchymal cells in the septum transversum. enclosing the embryonic liver, but not embryonic HSCs, expressed PTN mRNA. We suggest that PTN is secreted from activated adult HSCs and embryonic mesenchymal cells as a mitogen of paren-chymal cells in adult and embryonic liver, respectively.