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Studies on competence factors in hepatocyte proliferation

肝细胞增殖能力因素的研究

基本信息

批准号：
02670296
负责人：
HASHIMOTO Naoaki
金额：
$ 1.47万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

The studies on hepatocyte proliferation has been made great advance in recent years using primary cultures of hepatocytes. Several growth factors were anticipated that they played important roles in liver regeneration through their proliferative activities on hepatocytes., However, little is known about the "trigger" factor (s) of liver regeneration. It was reported that two kinds of growth factors acted sequentially in fibroblast proliferation : competence f-actor and progression factor. Although physiological coinpe-tence factor of hepatocytes has never been reported, it would probably be a trigger factor of liver regeneration because it can act on quiescent cells and can make them sensitive to progression factors.In the present studies, we found that the density of prostaglandin (PG) E_2 receptors on the rat hepa-Locytes in primary culture was decreased when cells were prepared from the rats received partial hepatectomy. We concluded that this decrease was the down regulation of PGE_2 receptors reflecting the direct exposure of the hepatocytes to PGE_2 in vivo after the surgery.In addition, we revealed that PGs had proliferative activities on hepatocyte in serum-free primary culture by enhancing their sensitivity to insulin plus epidermal growth factor. This activity was most prominent in PGE_2, and the action was mediated through stereo-specific PGE_2 receptor and pertusis toxin sensitive G-protein. PGF_2 alpha in higher concentration could act by cross-reacting to PGE_2 receptor. PG actions were, at least in part, mediated by the increase in the intracellular Ca^<2+> concentration. PGE_2 might be derived from sinusoldal endotherial cells, because cultured cells secreated PGE_2.In conclusion, PGE_2 was suggested to be a competence factor in hepatocyte proliferation, and to act as a trigger factor for liver regeneration.

近年来，利用原代培养的肝细胞进行肝细胞增殖的研究取得了很大进展。几种生长因子通过对肝细胞的增殖活性在肝再生中发挥重要作用，然而，对肝再生的“触发”因素知之甚少。据报道，在成纤维细胞增殖过程中，有两种生长因子依次起作用：感受态因子和进展因子。肝细胞的生理活性因子虽然未见报道，但由于它能作用于静止细胞，使其对生长因子敏感，故可能是肝再生的触发因子。结果表明，PGE_2受体表达下调，反映了术后肝细胞直接暴露于PGE_2，PGs对无血清原代培养的肝细胞具有促增殖作用，其作用机制可能与PGE_2增强肝细胞对胰岛素和表皮生长因子的敏感性有关。这种活性在PGE_2中最为显著，其作用是通过PGE_2受体和百日咳毒素敏感的G蛋白介导的。高浓度的PGF_2 α可与PGE_2受体发生交叉反应。PG的作用至少部分是由细胞内Ca^2+浓度的增加介导的。PGE_2可能来源于窦内皮细胞，因为培养的窦内皮细胞分泌PGE_2。因此，PGE_2可能是肝细胞增殖的活性因子，也可能是肝再生的触发因子。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hashimoto N, Watanabe T, Toda G, Ikeda Y, Yamada H, Yoshikawa Y, Mitsui H and Kurokawa K.: "Effects of prostaglandins on proliferation of hepatocytes in primary culture." hepatology. 12. 409 (1990)

Hashimoto N、Watanabe T、Toda G、Ikeda Y、Yamada H、Yoshikawa Y、Mitsui H 和 Kurokawa K.：“前列腺素对原代培养物中肝细胞增殖的影响”。

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Hashimoto N and Ikeda Y.: "Properties of prostagland in E_2 receptor in regenerating rat liver after partial hepatectomy. ----Studies using primary cultures." Jap J Gastroenterol. 87 (Suppl). 454 (1990)

Hashimoto N 和 Ikeda Y.：“部分肝切除术后再生大鼠肝脏中 E_2 受体前列腺的特性。----使用原代培养物的研究。”

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橋本直明,渡辺毅,戸田剛太郎,池田有成,山田春木,吉川雄二,光井洋,丸山稔之: "ラット無血清初代培養肝細胞の増殖に対するプロスタグランディンの効果" 肝臓. 31. 1244-1245 (1990)

Naoaki Hashimoto、Tsuyoshi Watanabe、Gotaro Toda、Arinari Ikeda、Haruki Yamada、Yuji Yoshikawa、Hiroshi Mitsui、Minoru Maruyama：“前列腺素对大鼠无血清原代培养肝细胞增殖的影响”31。1244-1245（1990）。