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Deletion of Golgi protein 73 delayed hepatocyte proliferation of mouse in the early stages of liver regeneration
Author(s) -
Wang Jianwen,
Ning Jing,
Qian Xiangjun,
Zhang Ting,
Yao Mingjie,
Wang Jie,
Chen Xiangmei,
Lu Fengmin
Publication year - 2021
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.15315
Subject(s) - liver regeneration , cyclin d1 , biology , hepatocyte , cancer research , regeneration (biology) , microbiology and biotechnology , cell cycle , pi3k/akt/mtor pathway , signal transduction , pathology , medicine , cell , biochemistry , in vitro
Background and Aim Golgi protein 73 (GP73) is a transmembrane protein that can promote the proliferation of cancer cells. However, the roles of GP73 in the proliferation of non‐malignant hepatocytes have rarely been investigated. Methods The wild‐type (GP73 +/+ ) and GP73 gene knockout mice (GP73 −/− ) were subject to 70% partial hepatectomy (PHx) to explore the involvement of GP73 in liver regeneration. Results After PHx, a significant increase of GP73 expression was observed in GP73 +/+ mouse liver. Noticeably, promoted recovery of liver mass was observed in GP73 −/− mouse at Day 1 after PHx, as showed by the liver/body weight ratio. RNA sequencing revealed that genes relevant to cell cycle and inflammation response in the residual liver tissues were severely suppressed with the deletion of GP73, particularly the inactivation of NF‐κB signal pathway in early phase of liver regeneration. In line with this, we do see the downregulation of cell cycle‐related protein including cyclin D1, p‐cyclin D1, β‐catenin, as well as interleukin 6, tumor necrosis factor‐α, CCl2, and CXCl10. In contrast, activation of mTOR signaling pathway was documented, accompanied with the histological hypertrophy of hepatocytes in GP73 −/− mouse. Conclusions Golgi protein 73 deletion leads to delayed response of liver regeneration and inflammation in the early stages of liver regeneration after PHx.