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BMP4 and Gremlin 1 ...
BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH
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- Baboota, Ritesh (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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- Rawshani, Aidin, 1991 (författare)
- Gothenburg University,Göteborgs universitet,Center for Cardiovascular and Metabolic Research (CMR),Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
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- Bonnet, Laurianne (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
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- Li, Xiangyu (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Yang, Hong (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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- Mardinoglu, Adil (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UK
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- Tchkonia, T. (författare)
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA
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- Kirkland, J. L. (författare)
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA
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- Hoffmann, A. (författare)
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), University of Leipzig and University Hospital Leipzig, Leipzig, Germany
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- Dietrich, A. (författare)
- Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Section of Bariatric Surgery, University Hospital Leipzig, Leipzig, Germany
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- Boucher, Jeremie (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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- Bluher, M. (författare)
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), University of Leipzig and University Hospital Leipzig, Leipzig, Germany
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- Smith, Ulf, 1943 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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(creator_code:org_t)
- 2022-08-22
- 2022
- Engelska.
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:8, s. 1007-21
- Relaterad länk:
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- The role of hepatic cell senescence in human non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is not well understood. To examine this, we performed liver biopsies and extensive characterization of 58 individuals with or without NAFLD/NASH. Here, we show that hepatic cell senescence is strongly related to NAFLD/NASH severity, and machine learning analysis identified senescence markers, the BMP4 inhibitor Gremlin 1 in liver and visceral fat, and the amount of visceral adipose tissue as strong predictors. Studies in liver cell spheroids made from human stellate and hepatocyte cells show BMP4 to be anti-senescent, anti-steatotic, anti-inflammatory and anti-fibrotic, whereas Gremlin 1, which is particularly highly expressed in visceral fat in humans, is pro-senescent and antagonistic to BMP4. Both senescence and anti-senescence factors target the YAP/TAZ pathway, making this a likely regulator of senescence and its effects. We conclude that senescence is an important driver of human NAFLD/NASH and that BMP4 and Gremlin 1 are novel therapeutic targets. Baboota et al. investigate senescence as a driver of human NAFLD/NASH and show the roles of BMP4 and its antagonist Gremlin 1 as anti-senescent and pro-senescent molecules, respectively.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Nyckelord
- nonalcoholic fatty liver
- morphogenetic protein 4
- promotes
- fibrosis
- yap
- pathway
- inflammation
- homeostasis
- expression
- steatosis
- Endocrinology & Metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Baboota, Ritesh
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Rawshani, Aidin, ...
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Bonnet, Lauriann ...
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Li, Xiangyu
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Yang, Hong
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Mardinoglu, Adil
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visa fler...
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Tchkonia, T.
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Kirkland, J. L.
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Hoffmann, A.
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Dietrich, A.
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Boucher, Jeremie
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Bluher, M.
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Smith, Ulf, 1943
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Gastroenterologi
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Nature Metabolis ...
- Av lärosätet
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Göteborgs universitet
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Kungliga Tekniska Högskolan