Transcriptional regulation of Hepatic Stellate Cell activation in NASH
| العنوان: | Transcriptional regulation of Hepatic Stellate Cell activation in NASH |
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| المؤلفون: | Kim Ravnskjaer, Henrik Dimke, Maria H. Hansen, Sonja S Hohmann, Susanne Mandrup, Sofie M. Bendixen, Bjørk Ditlev Larsen, Mike Krogh Terkelsen, Sönke Detlefsen, Ann-Britt Marcher |
| المصدر: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) Marcher, A-B, Bendixen, S M, Terkelsen, M K, Hohmann, S S, Hansen, M H, Larsen, B D, Mandrup, S, Dimke, H, Detlefsen, S & Ravnskjaer, K 2019, ' Transcriptional regulation of Hepatic Stellate Cell activation in NASH ', Scientific Reports, vol. 9, no. 1, 2324 . https://doi.org/10.1038/s41598-019-39112-6 |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Liver Cirrhosis, Male, Time Factors, Transcription, Genetic, Cell Plasticity, lcsh:Medicine, Context (language use), Fructose, Biology, Chronic liver disease, Article, Transcriptome, Proto-Oncogene Protein c-ets-1, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Non-alcoholic Fatty Liver Disease, medicine, Hepatic Stellate Cells, Animals, Humans, lcsh:Science, Multidisciplinary, lcsh:R, Feeding Behavior, medicine.disease, Hepatic stellate cell activation, digestive system diseases, Mice, Inbred C57BL, 030104 developmental biology, Gene Expression Regulation, Diet, Western, Core Binding Factor Alpha 2 Subunit, Hepatic stellate cell, Cancer research, lcsh:Q, Steatohepatitis, Hepatic fibrosis, 030217 neurology & neurosurgery |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 2045-2322 |
| DOI: | 10.1038/s41598-019-39112-6 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95179c8bbe35958e5e887901ab6b2c3e https://pubmed.ncbi.nlm.nih.gov/30787418 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....95179c8bbe35958e5e887901ab6b2c3e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-019-39112-6 |