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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6
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Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6

机译：骨形态发生蛋白2、4和9分别独立于Hfe，转铁蛋白受体2（Tfr2）和IL-6刺激鼠铁调素1的表达

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摘要

Recently, it has been suggested that hepcidin, a peptide involved in iron homeostasis, is regulated by bone morphogenetic proteins (BMPs), apparently by binding to hemojuvelin (Hjv) as a coreceptor and signaling through Smad4. We investigate the role of Hfe, Tfr2 (transferrin receptor 2), and IL-6 in BMP2-, BMP4-, and BMP9-stimulated up-regulation of murine hepcidin, because these molecules, like Hjv, are known to be involved in hepcidin signaling. We show that the BMP signaling pathway acts independently of Hfe, Tfr2, and IL-6: The response to BMP2, BMP4, and BMP9 is similar in isolated hepatocytes of wild-type, Hfe(-/-), IL-6(-/-), and Tfr2(m) mutant mice. The potency of different human BMPs in stimulating hepcidin transcription by murine primary hepatocytes is BMP9 > BMP4 > BMP2. However, in human HepG2 cells, BMP4 and BMP9 are equally potent, whereas BMP2 requires a higher dose to become an effective hepcidin activator. Moreover, all of the tested BMPs are more potent regulators of hepcidin than IL-6 and thus are the most potent known stimulators of hepcidin transcription.
机译：最近，有人提出，铁调和素铁肽铁调素（hepcidin）受骨形态发生蛋白（BMP）的调节，显然是通过结合作为共同受体的血juvelin（Hjv）并通过Smad4进行信号传导来进行的。我们调查Hfe，Tfr2（转铁蛋白受体2）和IL-6在BMP2-，BMP4-和BMP9刺激的鼠铁调素上调中的作用，因为已知这些分子（如Hjv）参与了铁调素信号。我们显示BMP信号通路独立于Hfe，Tfr2和IL-6：对BMP2，BMP4和BMP9的反应在野生型Hfe（-/-），IL-6（-）分离的肝细胞中相似/-）和Tfr2（m）突变小鼠。不同人BMP刺激鼠原代肝细胞转录Hepcidin的能力为BMP9> BMP4> BMP2。但是，在人类HepG2细胞中，BMP4和BMP9具有同等效力，而BMP2需要更高剂量才能成为有效的铁调素激活剂。此外，所有测试的BMPs都比IL-6更有效的调节铁调素，因此是已知的最有效的铁调素刺激剂。

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