Landschulz W, Thesleff I, Ekblom P
J Cell Biol. 1984 Feb;98(2):596-601. doi: 10.1083/jcb.98.2.596.
Of the different growth supplements used in chemically defined media, only transferrin is required for differentiation of tubules in the embryonic mouse metanephros. Since transferrin is an iron-carrying protein, we asked whether iron is crucial for tubulogenesis. Differentiation of metanephric tubules both in whole embryonic kidneys and in a transfilter system was studied. The tissues were grown in chemically defined media containing transferrin, apotransferrin, the metal-chelator complex ferric pyridoxal isonicotinoyl hydrazone (FePIH), and excesses of ferric ion. Although we found that apotransferrin was not as effective as iron-loaded transferrin in promoting proliferation in the differentiating kidneys, excess ferric ion at up to 100 microM, five times the normal serum concentration, could not promote differentiation or proliferation. However, iron coupled to the nonphysiological, lipophilic iron chelator, pyridoxal isonicotinoyl hydrazone, to form FePIH, could sustain levels of cell proliferation and tubulogenesis similar to those attained by transferrin. Thus, the role of transferrin in cell proliferation during tubulogenesis is solely to provide iron. Since FePIH apparently bypasses the receptor-mediated route of iron intake, the use of FePIH as a tool for investigating cell proliferation and its regulation is suggested.
在化学成分明确的培养基中使用的不同生长补充剂中，只有转铁蛋白是胚胎小鼠后肾中肾小管分化所必需的。由于转铁蛋白是一种铁转运蛋白，我们不禁要问铁对于肾小管形成是否至关重要。我们研究了整个胚胎肾脏和跨滤系统中后肾肾小管的分化情况。组织在含有转铁蛋白、脱铁转铁蛋白、金属螯合物复合物吡啶醛异烟酰腙铁（FePIH）以及过量铁离子的化学成分明确的培养基中生长。尽管我们发现脱铁转铁蛋白在促进分化中的肾脏增殖方面不如载铁转铁蛋白有效，但高达100微摩尔（正常血清浓度的五倍）的过量铁离子并不能促进分化或增殖。然而，与非生理性亲脂性铁螯合剂吡啶醛异烟酰腙结合形成FePIH的铁，能够维持与转铁蛋白所达到的水平相似的细胞增殖和肾小管形成水平。因此，转铁蛋白在肾小管形成过程中细胞增殖中的作用仅仅是提供铁。由于FePIH显然绕过了受体介导的铁摄入途径，建议将FePIH用作研究细胞增殖及其调节的工具。
