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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2020; 12(12): 1198-1210
Published online Dec 27, 2020. doi: 10.4254/wjh.v12.i12.1198
Published online Dec 27, 2020. doi: 10.4254/wjh.v12.i12.1198
Cyclin-dependent kinase inhibitors p21 and p27 function as critical regulators of liver regeneration following 90% hepatectomy in the rat
Nicolas Moniaux, Laurence Lacaze, Adélie Gothland, Alice Deshayes, Didier Samuel, Jamila Faivre, INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif 94800, France
Nicolas Moniaux, Laurence Lacaze, Adélie Gothland, Alice Deshayes, Didier Samuel, Jamila Faivre, Université Paris-Saclay, Faculté de Médecine Le Kremlin, Bicêtre 94270, France
Jamila Faivre, Department of Pôle de Biologie Médicale, Laboratoire d’Onco-Hématologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Paul-Brousse University Hospital, Villejuif 94800, France
Author contributions: Moniaux N, Lacaze L, and Gothland A performed most of the experiments and analyzed the data; Deshayes A helped with handling animal tissues and western blot analysis; Faivre J designed the experiments, analyzed the data, and supervised the research; Moniaux N, Faivre J, and Samuel D wrote the manuscript.
Institutional animal care and use committee statement: Animal studies were performed in compliance with the institutional and European Union guidelines for laboratory animal care and approved by the CE2A-03-CNRS-Orléans Ethics Committee (Accreditation No. 01417.01).
Conflict-of-interest statement: All authors declare that they have no conflicts of interest.
Data sharing statement: Technical appendices, statistical codes, and datasets are available from the corresponding author at nicolas.moniaux@inserm.fr . No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared in accordance with them.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nicolas Moniaux, PhD, Academic Research, Research Scientist, Senior Scientist, INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, 12-14 Ave Paul Vaillant-Couturier, Villejuif 94800, France. nicolas.moniaux@inserm.fr
Received: June 15, 2020
Peer-review started: June 15, 2020
First decision: July 30, 2020
Revised: August 26, 2020
Accepted: October 28, 2020
Article in press: October 28, 2020
Published online: December 27, 2020
Processing time: 185 Days and 15.9 Hours
Peer-review started: June 15, 2020
First decision: July 30, 2020
Revised: August 26, 2020
Accepted: October 28, 2020
Article in press: October 28, 2020
Published online: December 27, 2020
Processing time: 185 Days and 15.9 Hours
Core Tip
Core Tip: There is a current pandemic of obesity and diabetes and the chronic liver damages they cause, and the outcomes of patients undergoing liver mass reduction for malignant diseases are poor. To design efficient strategies that limit the risk of post-hepatectomy liver failure, we used a rat model to clarify the causes of death after enlarged liver resection. Compared with standard 2/3 hepatectomy, enlarged resection resulted in a loss of hepatocyte functional activities and impaired regenerative capacities, which were associated with an overexpression of p21 and p27 inhibitors. The use of extracorporeal support device with p21 and p27 should be considered for the management of severe liver failure following extended hepatectomy.