Research output per year
Research output per year
Ann-Britt Marcher, Sofie M Bendixen, Mike K Terkelsen, Sonja S Hohmann, Maria H Hansen, Bjørk D Larsen, Susanne Mandrup, Henrik Dimke, Sönke Detlefsen, Kim Ravnskjaer
Research output: Contribution to journal › Journal article › Research › peer-review
Non-alcoholic steatohepatitis (NASH) signified by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis is a growing cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. Hepatic fibrosis resulting from accumulation of extracellular matrix proteins secreted by hepatic myofibroblasts plays an important role in disease progression. Activated hepatic stellate cells (HSCs) have been identified as the primary source of myofibroblasts in animal models of hepatotoxic liver injury; however, so far HSC activation and plasticity have not been thoroughly investigated in the context of NASH-related fibrogenesis. Here we have determined the time-resolved changes in the HSC transcriptome during development of Western diet- and fructose-induced NASH in mice, a NASH model recapitulating human disease. Intriguingly, HSC transcriptional dynamics are highly similar across disease models pointing to HSC activation as a point of convergence in the development of fibrotic liver disease. Bioinformatic interrogation of the promoter sequences of activated genes combined with loss-of-function experiments indicates that the transcriptional regulators ETS1 and RUNX1 act as drivers of NASH-associated HSC plasticity. Taken together, our results implicate HSC activation and transcriptional plasticity as key aspects of NASH pathophysiology.
Original language | English |
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Article number | 2324 |
Journal | Scientific Reports |
Volume | 9 |
Issue number | 1 |
Number of pages | 55 |
ISSN | 2045-2322 |
DOIs | |
Publication status | Published - 20. Feb 2019 |
Research output: Thesis › Ph.D. thesis
Mandrup, S. (Head coordinator), Grøntved, L. (PI), Ravnskjær, K. (PI), Krag, A. (PI), Moestrup, S. K. (PI), Graversen, J. H. (Co-PI), Blagoev, B. (PI), Madsen, J. G. S. (Co-PI), Lauridsen, M. E. M. (Project participant), Thiele, M. (Project participant), Wernberg, C. W. (PhD student), Nielsen, R. (Project participant), Marcher, A.-B. (Project participant), Siersbæk, M. (Project participant), Mortensen, T. P. (Project participant), Sarvari, A. K. (Project participant), van Hauwaert, E. L. (PhD student), Avolio, F. (Project participant), Boel, F. (PhD student), Skytthe, M. K. (PhD student), Terkelsen, M. K. (PhD student), Bendixen, S. M. (PhD student), Dam, T. V. (PhD student), Hansen, D. (PhD student) & Elmelund-Præstekær, L. C. B. (Coordinator)
01/10/2017 → 30/09/2023
Project: Research