Modulation of insulin-like growth factor-II/mannose 6-phosphate receptors and transforming growth factor-beta 1 during liver regeneration.
Modulation of insulin-like growth factor-II/mannose 6-phosphate receptors and transforming growth factor-beta 1 during liver regeneration.
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DOI：
10.1016/s0021-9258(18)54592-0
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发表时间：
1991-11
期刊：
影响因子：
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通讯作者：
R. Jirtle;B. Carr;C. Scott
中科院分区：
文献类型：
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作者：
R. Jirtle;B. Carr;C. Scott
转化生长因子-β 1（TGF-β 1）是一种有效的有丝分裂抑制物质，被认为在肝再生过程中调节肝细胞增殖方面发挥重要作用。在这项调查中，我们已经表明，免疫组化，肝细胞含有显着的细胞内浓度的TGF-β 1后12小时的三分之二部分肝切除术。肝细胞TGF-β 1浓度的增加最初仅限于位于肝门静脉周围区域的那些细胞。然而，细胞内TGF-β 1的升高是短暂的，并且在36小时内，TGF-β 1阳性的肝细胞以波浪状的方式从门静脉周围到肝小叶的中央周围区域发生变化。到48小时，大多数肝细胞不再含有TGF-β 1。有趣的是，TGF-β 1的这种暂时性增加总是在肝细胞复制开始之前约3-6小时。由于TGF-β 1 mRNA已被证明在正常情况下和整个肝再生过程中不存在于肝细胞中，因此这些结果意味着细胞内TGF-β 1的增加是由摄取增加引起的。我们进一步表明，胰岛素样生长因子-II/甘露糖6-磷酸（IGF-II/Man-6-P）受体在肝再生过程中上调，并且该受体表达的增加共同定位于含有高浓度TGF-β 1的肝细胞中。潜伏的TGF-β 1磷酸甘露糖基糖蛋白复合物已显示与IGF-II/Man-6-P受体结合。因此，我们的数据是一致的假设，这种潜在的复合物是通过IGF-II/Man-6-P受体内化到细胞内的酸性前溶酶体/内体区室，在那里成熟的TGF-β 1分子可以被激活的潜在复合物的解离。
Transforming growth factor-beta 1 (TGF-beta 1) is a potent mito-inhibiting substance that is thought to play an important function in regulating hepatocyte proliferation during liver regeneration. In this investigation, we have shown by immunohistochemistry that hepatocytes containing significant intracellular concentrations of TGF-beta 1 12 h after a two-thirds partial hepatectomy. This increase in hepatocyte TGF-beta 1 concentration was initially confined to those cells that resided in the periportal region of the liver. The elevation of intracellular TGF-beta 1 was, however, transient, and within 36 h, the hepatocytes positive for TGF-beta 1 had changed in a wavelike fashion from the periportal to the pericentral region of the liver lobules. By 48 h, most hepatocytes no longer contained TGF-beta 1. Interestingly, this temporary increase in TGF-beta 1 always preceded the onset of hepatocyte replication by approximately 3-6 h. Since TGF-beta 1 mRNA has been shown to be absent from hepatocytes normally and throughout liver regeneration, these results imply that the increase in intracellular TGF-beta 1 resulted from an augmented uptake. We have further shown that the insulin-like growth factor-II/mannose 6-phosphate (IGF-II/Man-6-P) receptors were up-regulated during liver regeneration and that the increased expression of this receptor co-localized in those hepatocytes containing elevated concentrations of TGF-beta 1. The latent TGF-beta 1 phosphomannosyl glycoprotein complex has been shown to bind to the IGF-II/Man-6-P receptor. Therefore, our data are consistent with the hypothesis that this latent complex is internalized through the IGF-II/Man-6-P receptor to the intracellular acidic prelysosomal/endosomal compartments where the mature TGF-beta 1 molecule could be activated by dissociation from the latent complex.