P22 PD Dr. Zimmermann
Defining HGF/c-Met dependent diagnostic markers and novel therapeutic targets in NASH-development

The purpose of the here presented proposal is to investigate mechanisms of NASH fibrosis development in mice and humans. We will delineate the role of the HGF/c-Met pathway on a cellular level by using conditional c-Met knockout mice and by analysing the interaction with the anti-oxidative stress response. Findings from the mouse system will be translated into the human system with the aim to define novel genes, which are involved in the pathogenesis of the diseases. [...]

Publications

• Wirtz T. H. , Reuken P. A., Jansen C., Fischer P., Bergmann I., Backhaus C., Emontzpohl C., Reißing J., Brandt E. F., Koenen T. M., Schneider K. M., Schierwagen R., Brol M. J., Chang J., Zimmermann H. W., Köse-Vogel N., Eggermann T., Kurth I., Stoppe C., Bucala R., Bernhagen J., Praktiknjo M., Stallmach A., Trautwein C., Trebicka J., Bruns T., Berres M.-L. (2021): Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis. JHEP Reports, in press,
• Drescher H. K. , Schippers A., Rosenhain S., Gremse F., Bongiovanni L., de Bruin A., Eswaran S., Gallage S. U., Pfister D., Szydlowska M., Heikenwalder M., Weiskirchen S., Wagner N., Trautwein C., Weiskirchen R., Kroy D. C. (2020): L-Selectin/CD62L is a Key Driver of non-alcoholic Steatohepatitis in Mouse and Men. Cells, 9(5), 1106, [5.656]
• van Roeyen C. R. C. , Martin I. V., Drescher A., Schuett K. A., Hermert D., Raffetseder U., Otten S., Buhl E. M., Braun G., Kuppe C., Liehn E., Boor P., Weiskirchen R., Eriksson U., Gross O., Eitner F., Floege J., Ostendorf T. (2019): Identification of platelet-derived growth factor C as a mediator of both renal fibrosis and hypertension. Kidney Int, 95, 1103-1119, [8.000]
• Hansel C. , Erschfeld S., Baues M., Lammers T., Weiskirchen R., Trautwein C., Kroy D.C., Drescher H.K. (2019): The inhibitory T cell receptors PD1 and 2B4 are differentially regulated on CD4 and CD8 T cells in a mouse model of non-alcoholic steatohepatitis. Front Pharmacol, 10, 244, [3.845]
• Hansel C. , Erschfeld S., Baues M., Lammers T., Weiskirchen R., Trautwein C., Kroy D. C., Drescher H. K. (2019): The Inhibitory T Cell Receptors PD1 and 2B4 Are Differentially Regulated on CD4 and CD8 T Cells in a Mouse Model of Non-alcoholic Steatohepatitis. frontiers in Pharmacology, [3.845]
• Dutton Sackett S. , Otto T., Mohs A., Sander L. E., Strauch S., Streetz K.L., Kroy D. C., Trautwein C. (2019): Myeloid cells require gp130 signaling for protective anti-inflammatory functions during sepsis. The FASEB Journal, 33(5), [5.498]
• Drescher H. K. , Weiskirchen S., Weiskirchen R. (2019): Current status in testing for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Cells, 8, 845, [5.656]
• Drescher H. K. , Brandt E. F., Fischer P., Dreschers S., Schwendener R. A., Kowalska M. A., Canbay A., Wasmuth H. E., Weiskirchen R., Trautwein C., Berres M. L., Kroy D. C., Sahin H. (2019): “.” 10, 326, [3.201] (2019): Platelet Factor 4 Attenuates Experimental Acute Liver Injury in Mice. Front Physiol, 10, 326, [3.201]
• Drescher H. K. , Weiskirchen R., Fülöp A., Hopf C., Gonzáles de San Roman E., Huesgen P.F., de Bruin A., Christ A., Tolba R., Trautwein C., Kroy D.C. (2019): The influence of different fat sources on steatohepatitis and fibrosis development in the Western diet mouse model of non-alcoholic steatohepatitis (NASH). Front Physiol, 10, 770, [3.394]
• Drescher, H , Schippers, A., Clahsen, T., Sahin, H., Noels, H., Hornef, M., Wagner, N., Trautwein, C., Streetz, K.L., Kroy, D.C. (2017): β7-Integrin and MAdCAM-1 Play Opposing Roles During the Development of Non-Alcoholic Steatohepatitis. Journal of Hepatology, 66(6), 1251-1264, [10.590]
• Ramadori, P , Drescher, H., Erschfeld, S., Fragoulis, A., Kensler, T., Wruck, C., Cubero, J., Trautwein, C., Streetz, K., Kroy, D. (2017): Genetic Nrf2 over-activation inhibits the deleterious effects induced by hepatocyte specific c-met deletion during the progression of NASH. Oxidative Medicine and Cellular Longevity, [4.492]
• Hackstein CP , Assmus LM, Welz M, Klein S, Schwandt T, Schultze J, Förster I, Gondorf F, Beyer M, Kroy D, Kurts C, Trebicka J, Kastenmüller W, Knolle PA, Abdullah Z. (2016): Gut microbial translocation corrupts myeloid cell function to control bacterial infection during liver cirrhosis. Gut,, , 1-12, [14.921]
• Berres M.L. , Lehmann J, Jansen C, Görtzen J, Meyer C, Thomas D, Zimmermann HW, Kroy D, Schumacher F, Strassburg CP, Sauerbruch T, Trautwein C, Wasmuth HE, Trebicka J. (2016): Chemokine (C-X-C motif) ligand 11 levels predict survival in cirrhotic patients with transjugular intrahepatic portosystemic shunt. Liver Int., Mar, 36(3):386-94. doi: 10.1111/liv.12922. Epub 2015 Aug 17. PubMed PMID: 26212075., [4.470]
• Wertenbruch, S. , Drescher, H., Grossarth, V., Kroy, D., Giebeler, A., Erschfeld, S., Heinrichs, D., Soehnlein, O., Trautwein, C., Brandenburg, L.O., Streetz, K. (2015): The Anti-Microbial Peptide LL-37/CRAMP Is Elevated in Patients with Liver Diseases and Acts as a Protective Factor during Mouse Liver Injury.. Digestion, 91, 309-317, [1.884]
• Ramadori, P. , Drescher, H., Erschfeld, S., Schumacher, F., Berger, C., Fragoulis, A., Schenkel, J., Kensler, T.W., Wruck, C.J., Trautwein, C., Kroy, D.C., Streetz K.L. (2015): Hepatocyte-specific KEAP1 deletion reduces liver steatosis but not inflammation during non-alcoholic–steatohepatitis devolopment.. Free Radical Biol Med, 91, 114-26, [5.784]
• Ramadori, P (2015): Immunoregulation by lipids during the development of non-alcoholic steatohepatitis.. Hepatobiliary Surg Nutr, 4(1), 11-23, [3.050]
• Ramadori, P , Weiskirchen, R., Trebicka, J., Streetz, K. (2015): Mouse models of metabolic liver injury.. Lab Animals, 49(S1), 47-58., [1.553]
• Kroy, D. C. (2014): Hepatocyte specific deletion of c-Met leads to the development of severe non-alcoholic–steatohepatitis in mice.. Journal of Hepatology, 61 (4), 883-90, [10.590]
• Sahin, H. , Borkham-Kamphorst, E., do, O. N., Berres, M. L., Kaldenbach, M., Schmitz, P., Weiskirchen, R., Liedtke, C., Streetz, K. L., Maedler, K., Trautwein, C., Wasmuth, H. E. (2013): Proapoptotic effects of the chemokine, CXCL 10 are mediated by the noncognate receptor TLR4 in hepatocytes.. Hepatology, 57 (2), 797-805, [11.711]
• Liedtke, C. , Luedde T, Sauerbruch T, Scholten D, Streetz K, Tacke F, Tolba R, Trautwein C, Trebicka J, Weiskirchen R. (2013): Experimental liver fibrosis research: Update on animal models, legal issues and translational aspects.. Fibrogenesis & Tissue Repair, 6(1), 19, [2.329]
• Kaldenbach, M. , Giebeler, A., Tschaharganeh, D. F., Erschfeld, S., Wasmuth, H. E., Dolle, L., Floege, J., Trautwein, C., Streetz, K. L. (2012): Hepatocyte growth factor/c-Met signalling is important for the selection of transplanted hepatocytes. Gut, 61 (8), 1209-1218, [14.921]
• Schirin-Sokhan, R. , Winograd, R., Tischendorf, S., Wasmuth, H. E., Streetz, K., Tacke, F., Trautwein, C., Tischendorf, J. J. (2011): Assessment of inflammatory and fibrotic stenoses in patients with Crohn's disease using contrast-enhanced ultrasound and computerized algorithm: a pilot study. Digestion, 83, 263-268, [1.884]
• Liedtke, C. , Bangen, J. M., Freimuth, J., Beraza, N., Lambertz, D., Cubero, F. J., Hatting, M., Karlmark, K. R., Streetz, K. L., Krombach, G. A., Tacke, F., Gassler, N., Riethmacher, D., Trautwein, C. (2011): Loss of caspase-8 protects mice against inflammation-related hepatocarcinogenesis but induces non-apoptotic liver injury. Gastroenterology, 141 (6), 2176-2187, [18.187]
• Berres, M. L. , Koenen, R. R., Rueland, A., Zaldivar, M. M., Heinrichs, D., Sahin, H., Schmitz, P., Streetz, K. L., Berg, T., Gassler, N., Weiskirchen, R., Proudfoot, A., Weber, C., Trautwein, C., Wasmuth, H. E. (2010): Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice. Journal of Clinical Investigation, 120 (11), 4129-4140, [12.575]
• Zaldivar, M. M. , Pauels, K., von Hundelshausen, P., Berres, M. L., Schmitz, P., Bornemann, J., Kowalska, M. A., Gassler, N., Streetz, K. L., Weiskirchen, R., Trautwein, C., Weber, C., Wasmuth, H. E. (2010): CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis. Hepatology, 51 (4), 1345-1353, [11.711]