Splenectomy after partial hepatectomy accelerates liver regeneration in mice by promoting tight junction formation via polarity protein Par 3-aPKC
Splenectomy after partial hepatectomy accelerates liver regeneration in mice by promoting tight junction formation via polarity protein Par 3-aPKC
复制标题
部分肝切除术后的脾切除通过极性蛋白 Par 3-aPKC 促进紧密连接形成，加速小鼠肝脏再生
DOI：
10.1016/j.lfs.2017.11.032
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发表时间：
2018-01-01
期刊：
影响因子：
6.1
通讯作者：
Xu, Xundi
中科院分区：
文献类型：
--
作者：
Liu, Guoxing;Xie, Chengzhi;Xu, Xundi
目的：一些实验研究表明，切除脾脏加速肝部分切除术后的肝再生。而脾切除促进肝再生的机制是通过改善紧密连接的形成和肝细胞极性的建立。主要方法：我们分析了70%部分肝切除小鼠（PHx）和同时70%部分肝切除和脾切除小鼠（PHs）在预定时间点的细胞因子、基因和蛋白表达。关键发现：与PHx组相比，PHs组脾切除促进肝细胞增殖。闭合小带-1（ZO-1）的表达表明脾切除促进了肝再生过程中紧密连接的形成。TNF-α、IL-6、HGF、TSP-1和TGF-β 1是肝再生过程中紧密连接形成和肝细胞极性建立的必要因素。脾切除后，Par 3和aPKC调节肝细胞的定位和连接结构，提示TNF-α、IL-6、HGF、TSP-1和TGF-β 1的时程表达及血小板的变化参与了肝再生。联合脾切除可通过改善紧密连接的形成来加速肝再生，这可能有助于通过Par 3-aPKC建立肝细胞极性。这为肝癌肝部分切除和活体肝移植后脾切除能促进肝再生提供了线索。
Aims: Several experimental studies have demonstrated that removal of the spleen accelerates liver regeneration after partial hepatectomy. While the mechanism of splenectomy promotes liver regeneration by the improvement of the formation of tight junction and the establishment of hepatocyte polarity is still unknown.Main methods: We analyzed the cytokines, genes and proteins expression between 70% partial hepatectomy mice (PHx) and simultaneous 70% partial hepatectomy and splenectomy mice (PHs) at predetermined timed points.Key findings: Compared with the PHx group mice, splenectomy accelerated hepatocyte proliferation in PHs group. The expression of Zonula occludens-1 (ZO-1) indicated that splenectomy promotes the formation of tight junction during liver regeneration. TNF-alpha, IL-6, HGF, TSP-1 and TGF-beta 1 were essential factors for the formation of tight junction and the establishment of hepatocytes polarity in liver regeneration. After splenectomy, Partitioning defective 3 homolog (Par 3) and atypical protein kinase C (aPKC) regulate hepatocyte localization and junctional structures in regeneration liver.Significance: Our data suggest that the time course expression of TNF-alpha, IL-6, HGF, TSP-1, and TGF-beta 1 and the change of platelets take part in liver regeneration. Combination with splenectomy accelerates liver regeneration by improvement of the tight junction formation which may help to establish hepatocyte polarity via Par 3-aPKC. This may provide a clue for us that splenectomy could accelerate liver regeneration after partial hepatectomy of hepatocellular carcinoma and living donor liver transplantation.