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表达谱揭示了骨桥蛋白信号通路与大鼠肝脏再生在细胞水平上的相关性。

Expression profiles uncover the correlation of OPN signaling pathways with rat liver regeneration at cellular level.

作者信息

Wang Gaiping, Li Xiaofang, Chen Shasha, Zhao Weiming, Yang Jing, Chang Cuifang, Xu Cunshuan

机构信息

College of Life Science, Henan Normal University, Xinxiang, Henan, China.

State Key Laboratory Cultivation Base for Cell Differentiation Regulation, Henan Normal University, Xinxiang, China.

出版信息

Cell Biol Int. 2015 Nov;39(11):1329-40. doi: 10.1002/cbin.10523. Epub 2015 Aug 27.

DOI:10.1002/cbin.10523
PMID:26269331
Abstract

Osteopontin (OPN) could participate in the occurrence of multiple liver diseases via promoting inflammation, cell activation, proliferation, and migration. However, the correlation of OPN with liver regeneration (LR) is poorly defined. Previous studies from us and others revealed that OPN was probably involved in the activation and proliferation of various hepatic cell types during LR. In this study, to further investigate the underlined mechanism of OPN in regulating LR, eight hepatic cell types were isolated and purified from rat regenerative livers at 10 time points. The gene expression profiles of above hepatic cells were assayed by Rat Genome 230 2.0 chips, and then IPA software was used to uncover the correlations of gene expression changes with physiological activities. The findings demonstrated that the majority of the OPN pathway-related genes were up-regulated in hepatocytes (HCs), pit cells (PCs), oval cells (OCs), and biliary epithelial cells (BECs) but down-regulated in other four cell types including sinusoidal endothelial cells (SECs), Kupffer cells (KCs), dendritic cells (DCs), and hepatic stellate cells (HSCs). Thereafter, functional enriched analysis by IPA indicated that OPN signaling pathway might promote cell proliferation, activation, migration, and inflammation in HCs, OCs, BECs, and PCs, and slightly boost proliferation and migration of SECs and KCs but inhibit inflammation response and chemotaxis in SECs and KCs and almost all physiological processes in DCs and HSCs. Morever, apoptosis, cell death, and necrosis were remarkably inhibited through JAK/STAT, ERK1/2, and NF-kB branches in almost every cell type. These above results suggest that OPN signaling pathway is closely related to HCs, OCs, BECs, and PCs but has less regulatory effect on SECs, KCs, HSCs, and DCs during rat LR.

摘要

骨桥蛋白(OPN)可通过促进炎症、细胞活化、增殖和迁移参与多种肝脏疾病的发生。然而,OPN与肝再生(LR)的相关性尚不明确。我们和其他团队之前的研究表明,OPN可能参与了肝再生过程中各种肝细胞类型的活化和增殖。在本研究中,为了进一步探究OPN调节肝再生的潜在机制,在10个时间点从大鼠再生肝脏中分离并纯化了8种肝细胞类型。通过大鼠基因组230 2.0芯片检测上述肝细胞的基因表达谱,然后使用IPA软件揭示基因表达变化与生理活动之间的相关性。结果表明,大多数与OPN通路相关的基因在肝细胞(HCs)、pit细胞(PCs)、卵圆细胞(OCs)和胆管上皮细胞(BECs)中上调,但在其他四种细胞类型中下调,包括窦状内皮细胞(SECs)、库普弗细胞(KCs)、树突状细胞(DCs)和肝星状细胞(HSCs)。此后,IPA的功能富集分析表明,OPN信号通路可能促进HCs、OCs、BECs和PCs中的细胞增殖、活化、迁移和炎症,略微促进SECs和KCs的增殖和迁移,但抑制SECs和KCs中的炎症反应和趋化作用以及DCs和HSCs中的几乎所有生理过程。此外,几乎在每种细胞类型中,JAK/STAT、ERK1/2和NF-κB分支都显著抑制了细胞凋亡、细胞死亡和坏死。上述结果表明,在大鼠肝再生过程中,OPN信号通路与HCs、OCs、BECs和PCs密切相关,但对SECs、KCs、HSCs和DCs的调节作用较小。

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