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Int J Clin Exp Pathol 2013;6(9):1759-1769

Original Article
Limited therapeutic efficacy of thrombopoietin on the regeneration of steatotic livers

Kerstin Abshagen, Franziska Mertens, Christian Eipel, Brigitte Vollmar

Institute for Experimental Surgery, Rostock University Medical School, 18057 Rostock, Germany

Received July 1, 2013; Accepted July 23, 2013; Epub August 15, 2013; Published September 1, 2013

Abstract: Liver regeneration after partial hepatectomy is impaired in steatotic livers of leptin-deficient ob/ob mice. Previous studies have shown
that thrombopoietin (TPO) promotes liver regeneration and improves liver cirrhosis by an increase of platelet counts and the expansion of
hepatic progenitor cells. Herein we studied whether TPO exerts pro-proliferative and hepatoprotective effects and thereby improves the
regenerative capacity of steatotic livers. For this purpose, we studied hepatic regeneration at day 2, 3, 7 and 10 in a model of 55% hepatectomy
in obese (ob/ob) and non-obese (C57BL/6J) mice. Liver function and injury, platelet counts, weight of the regenerated liver, proliferating liver
cells as well as the number of hepatic (CK19-positive) oval cells were quantified by biochemical and immunohistochemical analysis. As
expected, obese mice had a markedly decreased regenerative capacity of livers compared with lean animals. Pretreatment of mice with
recombinant TPO (12.5 µg/kg) had no evident effect on regeneration of fatty livers, but ameliorated acute liver damage in obese mice, as
indicated by decreased liver enzyme release early after resection. TPO was unable to enhance hepatocyte proliferation, but increased
proliferation of non-parenchymal cells, including CK19-positive oval cells, at later observation time points after resection. Interestingly, TPO
completely inhibited the resection-induced increase of plasma triglycerides immediately after resection in non-obese mice. In conclusion, TPO
slightly prevents acute liver damage after resection in obese mice, but fails to significantly enhance regeneration of fatty livers. (IJCEP1307001).

Keywords: Thrombopoietin, partial hepatectomy, ob/ob, steatosis, oval cells

Address correspondence to: Dr. Kerstin Abshagen, Institute for Experimental Surgery, University of Rostock, Schillingallee 69a, 18057
Rostock, Germany. Tel: +49 381 494 2503; Fax: +49 381 494 2502; E-mail: kerstin.abshagen@uni-rostock.de