IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype
IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype
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DOI：
10.1002/2211-5463.12750
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发表时间：
2019-11
期刊：
影响因子：
2.6
通讯作者：
Tokio Sasaki;Yuji Suzuki;Keisuke Kakisaka;Ting Wang;K. Ishida;Akiko Suzuki;Hiroaki Abe;T. Sugai;Y. Takikawa
中科院分区：
文献类型：
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作者：
Tokio Sasaki;Yuji Suzuki;Keisuke Kakisaka;Ting Wang;K. Ishida;Akiko Suzuki;Hiroaki Abe;T. Sugai;Y. Takikawa
成年哺乳动物肝脏表现出显着的再生能力，根据损伤的类型和程度有不同的再生模式。肝细胞-胆管细胞双表型肝祖细胞群在过度损伤的情况下出现。据报道，成熟的肝细胞可以向胆管细胞表型转分化，并成为祖细胞群的细胞来源。在这里，我们确定在各种血浆细胞因子中，白介素（IL）-8水平在急性肝衰竭和严重急性肝损伤患者中显着升高。体外测定表明，给予 IL-8 同源物会增加 Sry HMG 盒蛋白 9 (SOX9) 的表达。在急性肝损伤患者的肝活检中，我们观察到 SOX9 阳性双表型肝细胞的出现，并伴有血浆 IL-8 水平升高。我们的结果表明，IL-8 调节成熟肝细胞向胆管细胞表型的表型转化。
The adult mammalian liver exhibits a remarkable regenerative capacity, with different modes of regeneration according to the type and extent of injury. Hepatocyte–cholangiocyte biphenotypic liver progenitor cell populations appear under conditions of excessive injury. It has been reported that mature hepatocytes can transdifferentiate toward a cholangiocyte phenotype and be a cellular source of progenitor cell populations. Here, we determined that among various plasma cytokines, interleukin (IL)‐8 levels were significantly elevated in acute liver failure and severe acute liver injury patients. In vitro assays revealed that administration of IL‐8 homologues increases the expression of Sry HMG box protein 9 (SOX9). In liver biopsies of acute liver injury patients, we observed the appearance of SOX9‐positive biphenotypic hepatocytes accompanied by elevation of plasma IL‐8 levels. Our results suggest that IL‐8 regulates the phenotypic conversion of mature hepatocytes toward a cholangiocyte phenotype.