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

Abstract

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 Akt 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, wemore » conclude that LASS2 plays an important role in efficient liver regeneration in response to PHx. - Highlights: • LASS2 remarkably increased during liver regeneration after PHx. • Liver regeneration is delayed by LASS2 knockout in mice. • Proliferation and cell cycle entry of hepatocytes after PHx is impaired by LASS2 knockout in mice. • Knockout of LASS2 activated Akt signaling and increased cell size of hepatocytes during liver regeneration.« less

Authors:
;  [1];  [1];  [1];  [2];  [3]; ;  [1];  [1];  [1];  [4];  [1];
  1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032 (China)
  2. Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu (China)
  3. Department of Critical Care Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032 (China)
  4. Department of Life Science, Imperial College, London (United Kingdom)
Publication Date:
OSTI Identifier:
22719143
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 493; Journal Issue: 3; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CYCLE; HEPATECTOMY; HYPERTROPHY; KNOCK-OUT REACTIONS; LIVER; LIVER CELLS; MICE; PHOSPHORYLATION; PROTEINS; REGENERATION

Citation Formats

Jin, Haojie, Wang, Cun, Gu, Dishui, Department of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, Guangdong, Zhang, Yurong, Fan, Shaohua, Xing, Shunpeng, Wang, Hui, Ruan, Haoyu, Yang, Cheng, Shanghai Medical College of Fudan University, Shanghai, Lv, Yuanyuan, Feng, Hugang, Yao, Ming, and others, and. Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.09.128.
Jin, Haojie, Wang, Cun, Gu, Dishui, Department of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, Guangdong, Zhang, Yurong, Fan, Shaohua, Xing, Shunpeng, Wang, Hui, Ruan, Haoyu, Yang, Cheng, Shanghai Medical College of Fudan University, Shanghai, Lv, Yuanyuan, Feng, Hugang, Yao, Ming, & others, and. Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy. United States. doi:10.1016/J.BBRC.2017.09.128.
Jin, Haojie, Wang, Cun, Gu, Dishui, Department of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, Guangdong, Zhang, Yurong, Fan, Shaohua, Xing, Shunpeng, Wang, Hui, Ruan, Haoyu, Yang, Cheng, Shanghai Medical College of Fudan University, Shanghai, Lv, Yuanyuan, Feng, Hugang, Yao, Ming, and others, and. Sat . "Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy". United States. doi:10.1016/J.BBRC.2017.09.128.
@article{osti_22719143,
title = {Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy},
author = {Jin, Haojie and Wang, Cun and Gu, Dishui and Department of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, Guangdong and Zhang, Yurong and Fan, Shaohua and Xing, Shunpeng and Wang, Hui and Ruan, Haoyu and Yang, Cheng and Shanghai Medical College of Fudan University, Shanghai and Lv, Yuanyuan and Feng, Hugang and Yao, Ming and others, and},
abstractNote = {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 Akt 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. - Highlights: • LASS2 remarkably increased during liver regeneration after PHx. • Liver regeneration is delayed by LASS2 knockout in mice. • Proliferation and cell cycle entry of hepatocytes after PHx is impaired by LASS2 knockout in mice. • Knockout of LASS2 activated Akt signaling and increased cell size of hepatocytes during liver regeneration.},
doi = {10.1016/J.BBRC.2017.09.128},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 493,
place = {United States},
year = {2017},
month = {11}
}