Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes.
Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes.
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DOI：
10.1016/s0002-9440(10)62292-4
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发表时间：
2005-03
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影响因子：
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通讯作者：
A. Okaya;J. Kitanaka;N. Kitanaka;M. Satake;Yuna Kim;K. Terada;T. Sugiyama;M. Takemura;J. Fujimoto;N. Terada;A. Miyajima;T. Tsujimura
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作者：
A. Okaya;J. Kitanaka;N. Kitanaka;M. Satake;Yuna Kim;K. Terada;T. Sugiyama;M. Takemura;J. Fujimoto;N. Terada;A. Miyajima;T. Tsujimura
当肝细胞因肝损伤而增殖被阻止时，肝脏卵圆细胞参与肝再生。为了阐明制瘤素 M (OSM) 在涉及卵圆细胞的肝脏再生中的作用，我们检测了 2-乙酰氨基芴/部分肝切除模型中正在再生的肝脏中 OSM 和 OSM 特异性受体 (OSM-R) 的表达。 OSM-R的表达水平随卵圆细胞的数量而变化，并且仅在卵圆细胞中观察到其表达。另一方面，OSM 在卵圆细胞和库普弗细胞中表达。为了检查 OSM 对卵圆细胞生长和分化的影响，将大鼠卵圆细胞 (OC15-5) 在表达大鼠 OSM cDNA 的 293T 细胞的条件培养基中孵育。这导致生长抑制、形态变化（微绒毛和具有发达细胞器的大细胞质）以及肝细胞标记物（白蛋白、酪氨酸氨基转移酶和色氨酸加氧酶）的表达。通过将专门针对大鼠 OSM-R 的小干扰 RNA 引入 OC15-5 细胞，消除了含有大鼠 OSM 的条件培养基的影响。这些结果表明OSM是诱导OC15-5细胞分化为肝细胞的关键介质，并表明OSM/OSM-R系统在卵圆细胞分化为肝细胞中至关重要，从而促进肝再生。
Oval cells of the liver participate in liver regeneration when hepatocytes are prevented from proliferating in response to liver damage. To clarify the role of oncostatin M (OSM) in the liver regeneration involving oval cells, we examined the expression of OSM and OSM-specific receptor (OSM-R) in the liver undergoing regeneration in the 2-acetylaminofluorene/partial hepatectomy model. Expression levels of OSM-R changed in correlation to the number of oval cells, and its expression was exclusively observed in oval cells. On the other hand, OSM was expressed in both oval cells and Kupffer cells. To examine the effect of OSM on the growth and differentiation of oval cells, rat oval cells (OC15-5) were incubated in conditioned medium of 293T cells expressing rat OSM cDNA. This resulted in suppression of growth, changes in morphology (microvilli and large cytoplasm with developed organelles), and expression of hepatocyte markers (albumin, tyrosine amino transferase, and tryptophan oxygenase). The effects of the conditioned medium with rat OSM were abrogated by introducing a small interfering RNA specifically targeting rat OSM-R into OC15-5 cells. These results indicate that OSM is a key mediator for inducing differentiation of OC15-5 cells into hepatocytes and suggest that the OSM/OSM-R system is pivotal in the differentiation of oval cells into hepatocytes, thereby promoting liver regeneration.