Depletion of Bone Marrow-Derived Fibrocytes Attenuates TAA-Induced Liver Fibrosis in Mice
Felix Hempel,
Martin Roderfeld,
Rajkumar Savai,
Akylbek Sydykov,
Karuna Irungbam,
Ralph Schermuly,
Robert Voswinckel,
Kernt Köhler,
Yury Churin,
Ladislau Kiss,
Jens Bier,
Jörn Pons-Kühnemann,
Elke Roeb
Affiliations
Felix Hempel
Department of Gastroenterology, Justus Liebig University, D-35392 Giessen, Germany
Martin Roderfeld
Department of Gastroenterology, Justus Liebig University, D-35392 Giessen, Germany
Rajkumar Savai
Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), D-61231 Bad Nauheim, Germany
Akylbek Sydykov
Department of Internal Medicine, Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University, D-35392 Giessen, Germany
Karuna Irungbam
Department of Gastroenterology, Justus Liebig University, D-35392 Giessen, Germany
Ralph Schermuly
Department of Internal Medicine, Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University, D-35392 Giessen, Germany
Robert Voswinckel
Department of Internal Medicine, Bürgerhospital, D-61169 Friedberg, Germany
Kernt Köhler
Institute of Veterinary Pathology, Justus Liebig University, D-35392 Giessen, Germany
Yury Churin
Department of Gastroenterology, Justus Liebig University, D-35392 Giessen, Germany
Ladislau Kiss
Department of Internal Medicine, Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University, D-35392 Giessen, Germany
Jens Bier
Department of Internal Medicine, Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University, D-35392 Giessen, Germany
Jörn Pons-Kühnemann
Institute of Medical Informatics, Justus Liebig University, D-35392 Giessen, Germany
Elke Roeb
Department of Gastroenterology, Justus Liebig University, D-35392 Giessen, Germany
Bone marrow-derived fibrocytes (FC) represent a unique cell type, sharing features of both mesenchymal and hematopoietic cells. FC were shown to specifically infiltrate the injured liver and participate in fibrogenesis. Moreover, FC exert a variety of paracrine functions, thus possibly influencing the disease progression. However, the overall contribution of FC to liver fibrosis remains unclear. We aimed to study the effect of a specific FC depletion, utilizing a herpes simplex virus thymidine kinase (HSV-TK)/Valganciclovir suicide gene strategy. Fibrosis was induced by oral thioacetamide (TAA) administration in C57BL/6J mice. Hepatic hydroxyproline content was assessed for the primary readout. The HSV-TK model enabled the specific depletion of fibrocytes. Hepatic hydroxyproline content was significantly reduced as a result of the fibrocyte ablation (−7.8%; 95% CI: 0.7−14.8%; p = 0.033), denoting a reduced deposition of fibrillar collagens. Lower serum alanine transaminase levels (−20.9%; 95% CI: 0.4−36.9%; p = 0.049) indicate a mitigation of liver-specific cellular damage. A detailed mode of action, however, remains yet to be identified. The present study demonstrates a relevant functional contribution of fibrocytes to chronic toxic liver fibrosis, contradicting recent reports. Our results emphasize the need to thoroughly study the biology of fibrocytes in order to understand their importance for hepatic fibrogenesis.
