Fouraschen SM, de Ruiter PE, Kwekkeboom J, de Bruin RW, Kazemier G, Metselaar HJ, Tilanus HW, van der Laan LJ, de Jonge J. mTOR signaling in liver regeneration: Rapamycin combined with growth factor treatment. World J Transplant 2013; 3(3): 36-47 [PMID: 24255881 DOI: 10.5500/wjt.v3.i3.36]
Corresponding Author of This Article
Dr. Luc JW van der Laan, Department of Surgery and Laboratory of Experimental Transplantation and Intestinal Surgery, Erasmus MC-University Medical Center, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. l.vanderlaan@erasmusmc.nl
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Original Article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Transplant. Sep 24, 2013; 3(3): 36-47 Published online Sep 24, 2013. doi: 10.5500/wjt.v3.i3.36
mTOR signaling in liver regeneration: Rapamycin combined with growth factor treatment
Suomi MG Fouraschen, Petra E de Ruiter, Jaap Kwekkeboom, Ron WF de Bruin, Geert Kazemier, Herold J Metselaar, Hugo W Tilanus, Luc JW van der Laan, Jeroen de Jonge
Suomi MG Fouraschen, Petra E de Ruiter, Ron WF de Bruin, Geert Kazemier, Hugo W Tilanus, Luc JW van der Laan, Jeroen de Jonge, Department of Surgery and Laboratory of Experimental Transplantation and Intestinal Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands
Jaap Kwekkeboom, Herold J Metselaar, Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands
Author contributions: van der Laan LJW and de Jonge J contributed equally to this study; Fouraschen SMG designed the study, performed the experiments, collected and analyzed the data and wrote the manuscript; de Ruiter PE performed experiments, collected and analyzed data and edited the manuscript; Kwekkeboom J and de Bruin RWF provided scientific input as well as analytic tools and edited the manuscript; Kazemier G, Metselaar HJ and Tilanus HW provided clinical and scientific input and edited the manuscript; van der Laan LJW and de Jonge J designed the study, analyzed data and wrote the manuscript.
Supported by Erasmus MC Grant and the Liver Research Foundation (SLO) Rotterdam
Correspondence to: Dr. Luc JW van der Laan, Department of Surgery and Laboratory of Experimental Transplantation and Intestinal Surgery, Erasmus MC-University Medical Center, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. l.vanderlaan@erasmusmc.nl
Telephone: +31-10-7032759 Fax: +31-10-7032793
Received: March 7, 2013 Revised: May 28, 2013 Accepted: June 18, 2013 Published online: September 24, 2013 Processing time: 170 Days and 0.1 Hours
Core Tip
Core tip: Interference of immunosuppressive medication with liver regeneration is a highly relevant issue for transplantation of small-for-size liver grafts. Inhibition of mammalian target of rapamycin (mTOR) represents an important immunosuppressive strategy after transplantation, yet as mTOR regulates cell proliferation and autophagy, concerns remain regarding a negative impact on regeneration. The exact role of mTOR signaling after living-donor liver transplantation is largely unknown. Here we report that mTOR inhibition by rapamycin severely impairs liver regeneration and increases autophagy after liver resection in mice. The most novel finding of this study is that this impaired regeneration can be partly reversed by treatment with exogenous growth factors.
