Bone Morphogenetic Protein-4 Induced Rat Hepatic Progenitor Cell (WB-F344 Cell) Differentiation Toward Hepatocyte Lineage
Bone Morphogenetic Protein-4 Induced Rat Hepatic Progenitor Cell (WB-F344 Cell) Differentiation Toward Hepatocyte Lineage
复制标题
骨形态发生蛋白-4诱导大鼠肝祖细胞（WB-F344细胞）向肝细胞谱系分化
DOI：
10.1002/jcp.21731
复制
发表时间：
2009-07-01
影响因子：
5.6
通讯作者：
Gong, Yuewen
中科院分区：
文献类型：
--
作者：
Fan, Jianghong;Shen, Hong;Gong, Yuewen
肝祖细胞是肝脏中的局部干细胞，它们可以根据不同的刺激分化为肝细胞或胆管细胞。这些刺激包括细胞外生长因子和细胞内转录因子。骨形态发生蛋白4（BMP 4）是转化生长因子β（TGF-β）超家族的成员，最早被鉴定为诱导骨骼肌异位成骨的生长因子。BMP-4在肝脏中的作用尚不清楚，尤其是其在肝祖细胞分化中的作用。用BMP 4刺激大鼠HPCs（WB-F344细胞），通过逆转录聚合酶链反应（RT-PCR）和Western印迹分析观察WB-F344细胞的分化。腺病毒递送的BMP 4和重组BMP 4都能够诱导肝细胞标志物如白蛋白、达特-1和G6 β的表达，但不能诱导胆管细胞标志物如β 4-整联蛋白和CK 19的表达。BMP 4诱导WB-F344细胞向肝细胞分化是通过增加Smad I和ERK 1/2的磷酸化介导的。此外，BMP 4还刺激转录因子-C/EBP-α的表达，其参与WB-F344细胞向肝细胞的分化。BMP 4能够刺激WB-F344细胞向肝细胞系分化。J.细胞。220：72-81，2009年。(C)2009 Wiley-Liss，Inc.
Hepatic progenitor cells are local stem cells in the liver and they can be differentiated into either hepatocytes or cholangiocytes depending on different stimulations. These stimulations include extracellular growth factors and intracellular transcription factors. Bone morphogenetic protein 4 (BMP4) is a member of transforming growth factor beta (TGF-beta) superfamily and was first identified as growth factor to induce ectopic bone formation from skeletal muscle. Role of BMP4 in the liver is still unclear especially its role in hepatic progenitor cells (HPCs) differentiation. BMP4 was used to stimulate rat HPCs (WB-F344 cells) and differentiation of WB-F344 cells was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. Both adenovirus delivered BMP4 and recombinant BMP4 were able to induce expression of hepatocyte markers such as albumin, TAT-1, and G6Pase but not cholangiocyte markers such as beta 4-integrin and CK 19. BMP4 induced differentiation of WB-F344 cells toward hepatocytes was mediated by increase in phosphorylation of Smad I and ERK 1/2. Moreover, BMP4 also stimulated expression of transcription factor-C/EBP-alpha, which involved in differentiation of WB-F344 cells toward hepatocytes. BMP4 is able to stimulate WB-F344 cells differentiation toward hepatocyte lineage. J. Cell. Physiol. 220: 72-81, 2009. (C) 2009 Wiley-Liss, Inc.