Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy

Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy
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LASS2 的肝脏特异性缺失延迟了部分肝切除术后小鼠肝脏的再生

DOI:
10.1016/j.bbrc.2017.09.128
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发表时间:
2017-11-25
影响因子:
3.1
通讯作者:
Qin, Wenxin
Qin, Wenxin
中科院分区:
生物学4区
文献类型:
--
作者:
Jin, Haojie;Wang, Cun;Qin, Wenxin

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The capacity of liver regeneration is critical for patients with liver diseases. However, cellular and molecular mechanisms of liver regeneration are still incompletely defined. Here, we assessed roles of LASS2 in liver regeneration following partial hepatectomy (PHx) in mice. Our results showed that protein level of LASS2 remarkably increased during liver regeneration after PHx in wildtype (WT) mice. Comparing to WT mice, liver regeneration index after PHx was significantly decreased from day 1 to day 5 in liver specific LASS2 knockout (LASS2-LKO) mice. Interestingly, liver mass of LASS2-LKO mice could sufficiently recover at day 14 after PHx. Immunohistochemistry (IHC) and western blot analyses revealed that proliferation markers, such as PCNA and Ki67, were potently reduced during liver regeneration in LASS2-LKO mice. In addition, several cell cycle related molecules, such as cyclin A, CDK2 and p-Rb, were decreased in LASS2-LKO mice after PHx. Co-immunoprecipitation assay further revealed a decreased formation of CDK4/cyclin D1 complex after PHx in LASS2-LKO mice. However, phosphorylation of Ala was significantly activated from day 2 after PHx in LASS2-LKO mice when compared with that in WT mice, which may explain the recovery of liver mass at the late stage of liver regeneration in LASS2-LKO mice. Taken together, we conclude that LASS2 plays an important role in efficient liver regeneration in response to PHx. (C) 2017 Elsevier Inc. All rights reserved.