Primary hepatocyte survival on non-integrin-recognizable matrices without the activation of Akt signaling
Primary hepatocyte survival on non-integrin-recognizable matrices without the activation of Akt signaling
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DOI：
10.1016/j.biomaterials.2006.10.008
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发表时间：
2007-02-01
期刊：
影响因子：
14
通讯作者：
Akaike, Toshihiro
中科院分区：
文献类型：
--
作者：
Hoshiba, Takashi;Nagahara, Hikaru;Akaike, Toshihiro
细胞与细胞外基质（extracellular matrix，ECM）相互作用的破坏导致肝细胞失巢凋亡（anoikis），因此通过ECM抑制细胞失巢凋亡是肝组织工程应用的必要条件。一般认为，整合素信号在肝细胞存活中起重要作用，尽管肝细胞在某些类型的非整合素可识别的基质上存活数天，如聚（N-对乙烯基苄基-4-O-β-D-吡喃半乳糖基-D-甘露酰胺）（PVLA）和聚-L-赖氨酸（PLL），而没有血清。从gld/gld小鼠分离的肝细胞的非贴壁培养中的失巢凋亡被抑制，表明Fas信号诱导肝细胞失巢凋亡。在整合素和非整合素可识别基质上的肝细胞贴壁培养中Fas的产生减少。Akt的激活几乎没有观察到在贴壁培养的肝细胞上的整合素可识别的矩阵，而激活发生在贴壁培养的整合素可识别的矩阵。在非整合素可识别基质上的肝细胞贴壁培养中，Akt对肝细胞存活没有贡献。为了延长PVLA基质上肝细胞的存活时间，激活Akt信号通路可能是一个很好的途径。(c)2006爱思唯尔有限公司版权所有。
The suppression of the detachment-induced cell death (anoikis) by the interaction between the cells and extracellular matrix (ECM) is necessary for the application of liver tissue engineering because the disruption of interaction with ECM leads hepatocytes to anoikis. It has been considered, in general, that integrin signal plays an important role in the hepatocyte survival although hepatocytes survive on some types of non-integrin-recognizable matrices, such as poly(N-p-vinylbenzyl-4-O-beta-D-galactopyranosyl-D-gluconamide) (PVLA) and poly-L-lysine (PLL) for several days without the serum. Anoikis was suppressed in the non-adherent culture of hepatocytes isolated from gld/gld mouse, indicating that Fas signal induces hepatocyte anoikis. Fas production is decreased in the adherent culture of hepatocytes on both integrin- and non-integrin-recognizable matrices. Akt activation was hardly observed in the adherent culture of hepatocytes on non-integrin-recognizable matrices whereas the activation occurred in the adherent culture on integrin-recognizable matrices. In the adherent culture of hepatocytes on non-integrin-recognizable matrices, Akt does not contribute to the hepatocyte survival. To prolong the viability of hepatocytes in the adherent culture on PVLA matrix on which hepatocytes maintain their functions for longer period than those on PLL matrix, it might be a good approach to activate Akt signaling pathway. (c) 2006 Elsevier Ltd. All rights reserved.