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Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis
Aplastic anaemia (AA) is a life‐threatening hematopoietic disorder characterized by hypoplasia and pancytopenia with increasing fat cells in the bone marrow (BM). The BM‐derived mesenchymal stem cells (MSCs) from AA are more susceptible to be induced into adipogenic differentiation compared with tha...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111807/ https://www.ncbi.nlm.nih.gov/pubmed/29993187 http://dx.doi.org/10.1111/jcmm.13761 |
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author | Liu, Lu‐Lu Liu, Lei Liu, Hai‐Hui Ren, Sai‐Sai Dou, Cui‐Yun Cheng, Pan‐Pan Wang, Cui‐Ling Wang, Li‐Na Chen, Xiao‐Li Zhang, Hao Chen, Ming‐Tai |
author_facet | Liu, Lu‐Lu Liu, Lei Liu, Hai‐Hui Ren, Sai‐Sai Dou, Cui‐Yun Cheng, Pan‐Pan Wang, Cui‐Ling Wang, Li‐Na Chen, Xiao‐Li Zhang, Hao Chen, Ming‐Tai |
author_sort | Liu, Lu‐Lu |
collection | PubMed |
description | Aplastic anaemia (AA) is a life‐threatening hematopoietic disorder characterized by hypoplasia and pancytopenia with increasing fat cells in the bone marrow (BM). The BM‐derived mesenchymal stem cells (MSCs) from AA are more susceptible to be induced into adipogenic differentiation compared with that from control, which may be causatively associated with the fatty BM and defective hematopoiesis of AA. Here in this study, we first demonstrated that levamisole displayed a significant suppressive effect on the in vitro adipogenic differentiation of AA BM‐MSCs. Mechanistic investigation revealed that levamisole could increase the expression of ZFP36L1 which was subsequently demonstrated to function as a negative regulator of adipogenic differentiation of AA BM‐MSCs through lentivirus‐mediated ZFP36L1 knock‐down and overexpression assay. Peroxisome proliferator‐activated receptor gamma coactivator 1 beta (PPARGC1B) whose 3′‐untranslated region bears adenine‐uridine‐rich elements was verified as a direct downstream target of ZFP36L1, and knock‐down of PPARGC1B impaired the adipogenesis of AA BM‐MSCs. Collectively, our work demonstrated that ZFP36L1‐mediated post‐transcriptional control of PPARGC1B expression underlies the suppressive effect of levamisole on the adipogenic differentiation of AA BM‐MSCs, which not only provides novel therapeutic targets for alleviating the BM fatty phenomenon of AA patients, but also lays the theoretical and experimental foundation for the clinical application of levamisole in AA therapy. |
format | Online Article Text |
id | pubmed-6111807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61118072018-09-01 Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis Liu, Lu‐Lu Liu, Lei Liu, Hai‐Hui Ren, Sai‐Sai Dou, Cui‐Yun Cheng, Pan‐Pan Wang, Cui‐Ling Wang, Li‐Na Chen, Xiao‐Li Zhang, Hao Chen, Ming‐Tai J Cell Mol Med Original Articles Aplastic anaemia (AA) is a life‐threatening hematopoietic disorder characterized by hypoplasia and pancytopenia with increasing fat cells in the bone marrow (BM). The BM‐derived mesenchymal stem cells (MSCs) from AA are more susceptible to be induced into adipogenic differentiation compared with that from control, which may be causatively associated with the fatty BM and defective hematopoiesis of AA. Here in this study, we first demonstrated that levamisole displayed a significant suppressive effect on the in vitro adipogenic differentiation of AA BM‐MSCs. Mechanistic investigation revealed that levamisole could increase the expression of ZFP36L1 which was subsequently demonstrated to function as a negative regulator of adipogenic differentiation of AA BM‐MSCs through lentivirus‐mediated ZFP36L1 knock‐down and overexpression assay. Peroxisome proliferator‐activated receptor gamma coactivator 1 beta (PPARGC1B) whose 3′‐untranslated region bears adenine‐uridine‐rich elements was verified as a direct downstream target of ZFP36L1, and knock‐down of PPARGC1B impaired the adipogenesis of AA BM‐MSCs. Collectively, our work demonstrated that ZFP36L1‐mediated post‐transcriptional control of PPARGC1B expression underlies the suppressive effect of levamisole on the adipogenic differentiation of AA BM‐MSCs, which not only provides novel therapeutic targets for alleviating the BM fatty phenomenon of AA patients, but also lays the theoretical and experimental foundation for the clinical application of levamisole in AA therapy. John Wiley and Sons Inc. 2018-07-11 2018-09 /pmc/articles/PMC6111807/ /pubmed/29993187 http://dx.doi.org/10.1111/jcmm.13761 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Liu, Lu‐Lu Liu, Lei Liu, Hai‐Hui Ren, Sai‐Sai Dou, Cui‐Yun Cheng, Pan‐Pan Wang, Cui‐Ling Wang, Li‐Na Chen, Xiao‐Li Zhang, Hao Chen, Ming‐Tai Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis |
title | Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis |
title_full | Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis |
title_fullStr | Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis |
title_full_unstemmed | Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis |
title_short | Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis |
title_sort | levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through zfp36l1‐ppargc1b axis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111807/ https://www.ncbi.nlm.nih.gov/pubmed/29993187 http://dx.doi.org/10.1111/jcmm.13761 |
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