Growth differentiation factor 11 attenuates liver fibrosis via expansion of liver progenitor cells
| العنوان: | Growth differentiation factor 11 attenuates liver fibrosis via expansion of liver progenitor cells |
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| المؤلفون: | Hildegard Büning, Xizhong Shen, Amar Deep Sharma, Michael Ott, Taihua Yang, Elmar Jaeckel, Guangqi Song, Tobias Cantz, Anna-Carina Weiss, Qinggong Yuan, Xuemei Jiang, Asha Balakrishnan, Michael Manns, Selina Möbus, Zhen Dai, Martin Bentler, Heike Bantel, Arndt Vogel, Andreas Kispert, Anna Saborowski, Ji-Min Zhu |
| المصدر: | Gut. 69:1104-1115 |
| بيانات النشر: | BMJ, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Gene Flow, Liver Cirrhosis, Male, Cirrhosis, Fluorescent Antibody Technique, Chronic liver disease, Mice, Fibrosis, Animals, Humans, Medicine, Progenitor cell, In Situ Hybridization, Mice, Inbred BALB C, business.industry, Stem Cells, Liver cell, Gastroenterology, Growth differentiation factor, medicine.disease, Up-Regulation, Growth Differentiation Factors, Disease Models, Animal, Liver, Bone Morphogenetic Proteins, Cancer research, Hepatic stellate cell, Stem cell, business |
| الوصف: | ObjectiveLiver fibrosis and cirrhosis resulting from chronic liver injury represent a major healthcare burden worldwide. Growth differentiation factor (GDF) 11 has been recently investigated for its role in rejuvenation of ageing organs, but its role in chronic liver diseases has remained unknown. Here, we investigated the expression and function of GDF11 in liver fibrosis, a common feature of most chronic liver diseases.DesignWe analysed the expression of GDF11 in patients with liver fibrosis, in a mouse model of liver fibrosis and in hepatic stellate cells (HSCs) as well as in other liver cell types. The functional relevance of GDF11 in toxin-induced and cholestasis-induced mouse models of liver fibrosis was examined by in vivo modulation of Gdf11 expression using adeno-associated virus (AAV) vectors. The effect of GDF11 on leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)+ liver progenitor cells was studied in mouse and human liver organoid culture. Furthermore, in vivo depletion of LGR5+ cells was induced by injecting AAV vectors expressing diptheria toxin A under the transcriptional control of Lgr5 promoter.ResultsWe showed that the expression of GDF11 is upregulated in patients with liver fibrosis and in experimentally induced murine liver fibrosis models. Furthermore, we found that therapeutic application of GDF11 mounts a protective response against fibrosis by increasing the number of LGR5+ progenitor cells in the liver.ConclusionCollectively, our findings uncover a protective role of GDF11 during liver fibrosis and suggest a potential application of GDF11 for the treatment of chronic liver disease. |
| تدمد: | 1468-3288 0017-5749 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5802726a426e3c9b8daaa02c00422188 https://doi.org/10.1136/gutjnl-2019-318812 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5802726a426e3c9b8daaa02c00422188 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14683288 00175749 |
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