Bohnenberger, Hanibal

[["dc.bibliographiccitation.firstpage","57"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical & Experimental Metastasis"],["dc.bibliographiccitation.lastpage","66"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Kauffels, Anne"],["dc.contributor.author","Kitzmüller, Marie"],["dc.contributor.author","Gruber, Andrea"],["dc.contributor.author","Nowack, Hannah"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Kuthning, Anja"],["dc.contributor.author","Sprenger, Thilo"],["dc.contributor.author","Czejka, Martin"],["dc.contributor.author","Ghadimi, Michael"],["dc.contributor.author","Sperling, Jens"],["dc.date.accessioned","2020-12-10T14:11:27Z"],["dc.date.available","2020-12-10T14:11:27Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s10585-019-09954-5"],["dc.identifier.eissn","1573-7276"],["dc.identifier.issn","0262-0898"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71079"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Hepatic arterial infusion of irinotecan and EmboCept® S results in high tumor concentration of SN-38 in a rat model of colorectal liver metastases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","48"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","61"],["dc.bibliographiccitation.volume","199"],["dc.contributor.author","Klaßen, Carina"],["dc.contributor.author","Karabinskaya, Anna"],["dc.contributor.author","Dejager, Lien"],["dc.contributor.author","Vettorazzi, Sabine"],["dc.contributor.author","Van Moorleghem, Justine"],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Meijsing, Sebastiaan H."],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Libert, Claude"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2020-12-10T18:47:42Z"],["dc.date.available","2020-12-10T18:47:42Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.4049/jimmunol.1601691"],["dc.identifier.eissn","1550-6606"],["dc.identifier.issn","0022-1767"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78852"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model of Allergic Asthma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","549"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cancer Cell"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Mohr, Sebastian"],["dc.contributor.author","Döbele, Carmen"],["dc.contributor.author","Comoglio, Federico"],["dc.contributor.author","Berg, Tobias"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Alexe, Gabriela"],["dc.contributor.author","Corso, Jasmin"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Wachter, Astrid"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Schnuetgen, Frank"],["dc.contributor.author","Cremer, Anjali"],["dc.contributor.author","Haetscher, Nadine"],["dc.contributor.author","Goellner, Stefanie"],["dc.contributor.author","Rouhi, Arefeh"],["dc.contributor.author","Palmqvist, Lars"],["dc.contributor.author","Rieger, Michael A."],["dc.contributor.author","Schroeder, Timm"],["dc.contributor.author","Boenig, Halvard"],["dc.contributor.author","Meuller-Tidow, Carsten"],["dc.contributor.author","Kuchenbauer, Florian"],["dc.contributor.author","Schuetz, Ekkehard"],["dc.contributor.author","Green, Anthony R."],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Stegmaier, Kimberly"],["dc.contributor.author","Humphries, R. Keith"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Oellerich, Thomas"],["dc.date.accessioned","2018-11-07T10:25:02Z"],["dc.date.available","2018-11-07T10:25:02Z"],["dc.date.issued","2017"],["dc.description.abstract","The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho) proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU. 1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia."],["dc.identifier.doi","10.1016/j.ccell.2017.03.001"],["dc.identifier.isi","000398670600010"],["dc.identifier.pmid","28399410"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14438"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42772"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","1878-3686"],["dc.relation.issn","1535-6108"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S1448"],["dc.bibliographiccitation.issue","S15"],["dc.bibliographiccitation.journal","Journal of Thoracic Disease"],["dc.bibliographiccitation.lastpage","S1457"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Dinter, Helen"],["dc.contributor.author","König, Alexander"],["dc.contributor.author","Ströbel, Philipp"],["dc.date.accessioned","2020-12-10T18:42:54Z"],["dc.date.available","2020-12-10T18:42:54Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.21037/jtd.2017.02.02"],["dc.identifier.eissn","2077-6624"],["dc.identifier.issn","2072-1439"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78124"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Neuroendocrine tumors of the thymus and mediastinum"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e16712"],["dc.bibliographiccitation.issue","31"],["dc.bibliographiccitation.journal","Medicine"],["dc.bibliographiccitation.volume","98"],["dc.contributor.author","Buentzel, Judith"],["dc.contributor.author","Yao, Sha"],["dc.contributor.author","Elakad, Omar"],["dc.contributor.author","Lois, Anna-Maria"],["dc.contributor.author","Brünies, Jana"],["dc.contributor.author","König, Julia"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Emmert, Alexander"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.date.accessioned","2019-08-09T06:40:34Z"],["dc.date.available","2019-08-09T06:40:34Z"],["dc.date.issued","2019"],["dc.description.abstract","Molecular characterization of lung cancer specimens after radical surgery offers additional prognostic information and may help to guide adjuvant therapeutic procedures. The transcriptional regulators alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) have recently been described in different cancer entities as a useful prognostic biomarker. This study was initiated to explore their protein expression patterns and prognostic value in patients with operable lung cancer disease.The protein abundance (in the following text also named protein expression) of ATRX and DAXX were analyzed by immunohistochemistry in 194 samples of squamous cell lung carcinoma (SQCLC), 111 samples of pulmonary adenocarcinoma (AC) and 40 samples of small cell lung cancer (SCLC). The protein levels of ATRX and DAXX were correlated with clinicopathological characteristics and patient outcome.ATRX showed strong protein expression in 16.2% of AC, 11.9% of SQCLC, and 42.5% of SCLC. DAXX was highly expressed in 54.9% of AC, 76.2% of SQCLC, and 82.5% of SCLC. Immunostaining of both ATRX and DAXX were seen in 14.4% of AC, 11.3% of SQCLC, and 42.5% of SCLC. High protein expression of ATRX was a favorable prognostic marker for patients with AC (hazard ratio 0.38, P = .02). Sub-group analyses showed a significant correlation between ATRX and the clinical stage of SQCLC and SCLC. Histological grading and ATRX were also significantly associated in cases of SQCLC.The presence of ATRX and DAXX are correlated with lung cancer histology. Strong ATRX protein expression is associated with a significantly longer overall survival in patients with AC."],["dc.description.sponsorship","Open-Access-Publikationafonds 2019"],["dc.identifier.doi","10.1097/MD.0000000000016712"],["dc.identifier.pmid","31374064"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16343"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62353"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1536-5964"],["dc.relation.issn","0025-7974"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Expression and prognostic impact of alpha thalassemia/mental retardation X-linked and death domain-associated protein in human lung cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1220"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","1233"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Kaiser, Tina K."],["dc.contributor.author","Li, Hu"],["dc.contributor.author","Roßmann, Laura"],["dc.contributor.author","Reichardt, Sybille D."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Feldmann, Claus"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2021-04-14T08:27:15Z"],["dc.date.available","2021-04-14T08:27:15Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Glucocorticoids (GCs) are widely used to treat acute graft‐versus‐host disease (aGvHD) due to their immunosuppressive activity, but they also reduce the beneficial graft‐versus‐leukemia (GvL) effect of the allogeneic T cells contained in the graft. Here, we tested whether aGvHD therapy could be improved by delivering GCs with the help of inorganic–organic hybrid nanoparticles (IOH‐NPs) that preferentially target myeloid cells. IOH‐NPs containing the GC betamethasone (BMP‐NPs) efficiently reduced morbidity, mortality, and tissue damage in a totally MHC mismatched mouse model of aGvHD. Therapeutic activity was lost in mice lacking the GC receptor (GR) in myeloid cells, confirming the cell type specificity of our approach. BMP‐NPs had no relevant systemic activity but suppressed cytokine and chemokine gene expression locally in the small intestine, which presumably explains their mode of action. Most importantly, BMP‐NPs delayed the development of an adoptively transferred B cell lymphoma better than the free drug, although the overall incidence was unaffected. Our findings thus suggest that employing IOH‐NPs could diminish the risk of relapse associated with GC therapy of aGvHD patients while still allowing to efficiently ameliorate the disease."],["dc.description.abstract","Clinical symptoms and histological hallmarks of acute graft‐versus‐host disease in mice are ameliorated by glucocorticoids when specifically delivered to macrophages with the help of nanoparticles. In addition, this therapeutic intervention improves the graft‐versus‐leukemia effect compared to the free drug, and thus presumably reduces the risk of relapse. image"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1002/eji.201948464"],["dc.identifier.eissn","1521-4141"],["dc.identifier.issn","0014-2980"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82221"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Glucocorticoids delivered by inorganic–organic hybrid nanoparticles mitigate acute graft‐versus‐host disease and sustain graft‐versus‐leukemia activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Henric-Petri, Hannah"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Emmert, Alexander"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Strecker, Jasmin"],["dc.contributor.author","Holland, Rainer"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Corso, Jasmin"],["dc.contributor.author","Wagner, Sebastian"],["dc.contributor.author","Kueffer, Stefan"],["dc.contributor.author","Sebastian, Martin"],["dc.contributor.author","Bergmann, Lothar"],["dc.contributor.author","Danner, Bernd"],["dc.contributor.author","Schoendube, Friedrich Albert"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Oellerich, Thomas"],["dc.date.accessioned","2018-11-07T09:33:49Z"],["dc.date.available","2018-11-07T09:33:49Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1158/1538-7445.AM2014-2487"],["dc.identifier.isi","000349906903219"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32050"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","105th Annual Meeting of the American-Association-for-Cancer-Research (AACR)"],["dc.relation.eventlocation","San Diego, CA"],["dc.relation.issn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","Comprehensive quantitative proteomic profiling of lung cancers reveals novel biomarkers and potential drug targets"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2523"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Translational Lung Cancer Research"],["dc.bibliographiccitation.lastpage","2538"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Yao, Sha"],["dc.contributor.author","Peng, Luogen"],["dc.contributor.author","Elakad, Omar"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Hammerstein-Equord, Alexander von"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.date.accessioned","2021-08-12T07:45:40Z"],["dc.date.available","2021-08-12T07:45:40Z"],["dc.date.issued","2021"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.21037/tlcr-20-1039"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88522"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation.eissn","2226-4477"],["dc.relation.issn","2218-6751"],["dc.relation.orgunit","Institut für Pathologie"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","One carbon metabolism in human lung cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","21"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cancer Cell"],["dc.bibliographiccitation.lastpage","36.e13"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Goveia, Jermaine"],["dc.contributor.author","Rohlenova, Katerina"],["dc.contributor.author","Taverna, Federico"],["dc.contributor.author","Treps, Lucas"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Pircher, Andreas"],["dc.contributor.author","Geldhof, Vincent"],["dc.contributor.author","de Rooij, Laura P.M.H."],["dc.contributor.author","Kalucka, Joanna"],["dc.contributor.author","Sokol, Liliana"],["dc.contributor.author","García-Caballero, Melissa"],["dc.contributor.author","Zheng, Yingfeng"],["dc.contributor.author","Qian, Junbin"],["dc.contributor.author","Teuwen, Laure-Anne"],["dc.contributor.author","Khan, Shawez"],["dc.contributor.author","Boeckx, Bram"],["dc.contributor.author","Wauters, Els"],["dc.contributor.author","Decaluwé, Herbert"],["dc.contributor.author","De Leyn, Paul"],["dc.contributor.author","Vansteenkiste, Johan"],["dc.contributor.author","Weynand, Birgit"],["dc.contributor.author","Sagaert, Xavier"],["dc.contributor.author","Verbeken, Erik"],["dc.contributor.author","Wolthuis, Albert"],["dc.contributor.author","Topal, Baki"],["dc.contributor.author","Everaerts, Wouter"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Emmert, Alexander"],["dc.contributor.author","Panovska, Dena"],["dc.contributor.author","De Smet, Frederik"],["dc.contributor.author","Staal, Frank J.T."],["dc.contributor.author","Mclaughlin, Rene J."],["dc.contributor.author","Impens, Francis"],["dc.contributor.author","Lagani, Vincenzo"],["dc.contributor.author","Vinckier, Stefan"],["dc.contributor.author","Mazzone, Massimiliano"],["dc.contributor.author","Schoonjans, Luc"],["dc.contributor.author","Dewerchin, Mieke"],["dc.contributor.author","Eelen, Guy"],["dc.contributor.author","Karakach, Tobias K."],["dc.contributor.author","Yang, Huanming"],["dc.contributor.author","Wang, Jian"],["dc.contributor.author","Bolund, Lars"],["dc.contributor.author","Lin, Lin"],["dc.contributor.author","Thienpont, Bernard"],["dc.contributor.author","Li, Xuri"],["dc.contributor.author","Lambrechts, Diether"],["dc.contributor.author","Luo, Yonglun"],["dc.contributor.author","Carmeliet, Peter"],["dc.date.accessioned","2020-12-10T14:22:57Z"],["dc.date.available","2020-12-10T14:22:57Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.ccell.2019.12.001"],["dc.identifier.issn","1535-6108"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71785"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2561"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Gut"],["dc.bibliographiccitation.lastpage","2573"],["dc.bibliographiccitation.volume","71"],["dc.contributor.affiliation","Latif, Muhammad Umair; \r\n1\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Schmidt, Geske Elisabeth; \r\n1\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Mercan, Sercan; \r\n1\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Rahman, Raza; \r\n2\r\nGastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"],["dc.contributor.affiliation","Gibhardt, Christine Silvia; \r\n3\r\nMolecular Physiology, Institute of Cardiovascular Physiology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Stejerean-Todoran, Ioana; \r\n3\r\nMolecular Physiology, Institute of Cardiovascular Physiology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Reutlinger, Kristina; \r\n1\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Hessmann, Elisabeth; \r\n1\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Singh, Shiv K; \r\n1\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Moeed, Abdul; \r\n4\r\nInstitute for Microbiology and Hygiene, Medical Center-University of Freiburg, Freiburg, Baden-Württemberg, Germany"],["dc.contributor.affiliation","Rehman, Abdul; \r\n5\r\nInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Butt, Umer Javed; \r\n6\r\nClinical Neuroscience, Max-Planck-Institute for Experimental Medicine, Goettingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Bohnenberger, Hanibal; \r\n7\r\nInstitute of Pathology, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Stroebel, Philipp; \r\n7\r\nInstitute of Pathology, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Bremer, Sebastian Christopher; \r\n1\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Neesse, Albrecht; \r\n1\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Bogeski, Ivan; \r\n3\r\nMolecular Physiology, Institute of Cardiovascular Physiology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.affiliation","Ellenrieder, Volker; \r\n1\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Niedersachsen, Germany"],["dc.contributor.author","Latif, Muhammad Umair"],["dc.contributor.author","Schmidt, Geske Elisabeth"],["dc.contributor.author","Mercan, Sercan"],["dc.contributor.author","Rahman, Raza"],["dc.contributor.author","Gibhardt, Christine Silvia"],["dc.contributor.author","Stejerean-Todoran, Ioana"],["dc.contributor.author","Reutlinger, Kristina"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Moeed, Abdul"],["dc.contributor.author","Rehman, Abdul"],["dc.contributor.author","Butt, Umer Javed"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Bremer, Sebastian Christopher"],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Bogeski, Ivan"],["dc.contributor.author","Ellenrieder, Volker"],["dc.date.accessioned","2022-12-07T08:25:00Z"],["dc.date.available","2022-12-07T08:25:00Z"],["dc.date.issued","2022-04-01"],["dc.date.updated","2022-12-07T00:46:04Z"],["dc.description.abstract","ObjectivesNon-alcoholic fatty liver disease (NAFLD) can persist in the stage of simple hepatic steatosis or progress to steatohepatitis (NASH) with an increased risk for cirrhosis and cancer. We examined the mechanisms controlling the progression to severe NASH in order to develop future treatment strategies for this disease.DesignNFATc1 activation and regulation was examined in livers from patients with NAFLD, cultured and primary hepatocytes and in transgenic mice with differential hepatocyte-specific expression of the transcription factor (Alb-cre, NFATc1c.a\r\n. and NFATc1Δ/Δ\r\n). Animals were fed with high-fat western diet (WD) alone or in combination with tauroursodeoxycholic acid (TUDCA), a candidate drug for NAFLD treatment. NFATc1-dependent ER stress-responses, NLRP3 inflammasome activation and disease progression were assessed both in vitro and in vivo.ResultsNFATc1 expression was weak in healthy livers but strongly induced in advanced NAFLD stages, where it correlates with liver enzyme values as well as hepatic inflammation and fibrosis. Moreover, high-fat WD increased NFATc1 expression, nuclear localisation and activation to promote NAFLD progression, whereas hepatocyte-specific depletion of the transcription factor can prevent mice from disease acceleration. Mechanistically, NFATc1 drives liver cell damage and inflammation through ER stress sensing and activation of the PERK-CHOP unfolded protein response (UPR). Finally, NFATc1-induced disease progression towards NASH can be blocked by TUDCA administration.ConclusionNFATc1 stimulates NAFLD progression through chronic ER stress sensing and subsequent activation of terminal UPR signalling in hepatocytes. Interfering with ER stress-responses, for example, by TUDCA, protects fatty livers from progression towards manifest NASH."],["dc.description.sponsorship","the Volkswagen-Stiftung"],["dc.description.sponsorship","http://dx.doi.org/10.13039/501100001659Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship","German Cancer Aid"],["dc.identifier","35365570"],["dc.identifier.doi","10.1136/gutjnl-2021-325013"],["dc.identifier.pmid","35365570"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118455"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/173"],["dc.language.iso","en"],["dc.publisher","BMJ Publishing Group Ltd and British Society of Gastroenterology"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P17: Die Rolle mitochondrialer Kontaktstellen im Rahmen tumorrelevanter Calcium- und Redox-Signalwege"],["dc.relation.eissn","1468-3288"],["dc.relation.issn","0017-5749"],["dc.relation.workinggroup","RG Bogeski"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","http://creativecommons.org/licenses/by-nc/4.0/"],["dc.title","NFATc1 signaling drives chronic ER stress responses to promote NAFLD progression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]