Ethanolamine is a co-mitogenic factor for proliferation of primary hepatocytes
Ethanolamine is a co-mitogenic factor for proliferation of primary hepatocytes
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DOI：
10.1002/jcb.10012
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发表时间：
2002-01-01
影响因子：
4
通讯作者：
Watanabe, Y
中科院分区：
文献类型：
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作者：
Ajioka, I;Akaike, T;Watanabe, Y
成熟的成年实质肝细胞在肝细胞生长因子、表皮生长因子等生长因子存在的情况下可以进入S期，但在培养中几乎不能增殖。我们假设培养的肝细胞周期被限制在G(2)/M期之前，并试图确定诱导细胞周期进程的因素。我们发现，长期培养的肝细胞条件培养液与其他生长因子具有共促有丝分裂活性，这归因于乙醇胺(ETN)。ETN在多种生长因子的作用下，不仅能诱导肝细胞DNA合成，还能诱导细胞复制。ETN和HGF协同诱导细胞周期蛋白D-1、A和B的表达，但只有细胞周期蛋白B而不是细胞周期蛋白A与Cdc2形成复合体。此外，ETN联合HGF可促进PKCβII的表达，并将PKCβII移位至质膜，并诱导丝状足的形成，这一作用可被PKCβII的反义寡核苷酸抑制。此外，用细胞骨架重排抑制剂(秋水仙碱、细胞松弛素D或PKC特异性抑制剂)阻断细胞骨架重排，可抑制细胞周期蛋白的表达和细胞增殖。尽管ETN增强了下游产物细胞磷脂酰乙醇胺(PE)，但PE本身在肝细胞上并不显示任何ETN样活性。综上所述，我们的结果表明，在生长因子存在的情况下，ETN作为一种共复制因子促进成熟肝细胞的细胞周期进入G(2)/M期。这种活性被认为是由PKCβII依赖的细胞周期蛋白S的表达所介导的。(C)2001年Wiley-Liss，Inc.
Mature adult parenchymal hepatocytes can enter the S phase in the presence of growth factors such as HGF and EGF, but rarely proliferate in culture. We hypothesized that the cell cycle of hepatocytes in culture is restricted before G(2)/M phase and we attempted to identify the factor that induces cell cycle progression. We found that the conditioned medium from long-term cultured hepatocytes contained co-mitogenic activity with other growth factors, which was attributed to ethanolamine (Etn). Etn induced not only DNA synthesis but also cell replication of cultured hepatocytes with various other growth factors. Etn and HGF synergistically induced cyclin D-1, A and B expression, however, only cyclin B but not cyclin A formed a complex with Cdc2. In addition, Etn combined with HGF enhanced PKC beta II expression and translocated PKC beta II to the plasma membrane, and induced filopodia formation, which was inhibited by an antisense oligonucleotide against PKC beta II. In addition, blocking the cytoskeleton rearrangement with inhibitors (colchicine, cytochalasin D, or chlerythrine (a specific PKC inhibitor)) inhibited cyclin expression and cell proliferation. Although Etn enhanced the downstream product, cellular phosphatidylethanolamine (PE), PE itself did not show any Etn-like activities on hepatocytes. Taken together, our results indicate that Etn functions as a co-replication factor to promote the cell cycle of mature hepatocytes to G(2)/M phase in the presence of growth factors. The activity is thought to be mediated by PKC beta II-dependent cyclin S expression. (C) 2001 Wiley-Liss, Inc.