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BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway

Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis...

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Autores principales: Zhangdi, Hanjing, Geng, Xinyu, Li, Ning, Xu, Ruiling, Hu, Ying, Liu, Jingyang, Zhang, Xu, Qi, Jihan, Tian, Yingying, Qiu, Jiawei, Huang, Shiling, Cang, Xueyu, Jin, Shizhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618771/
https://www.ncbi.nlm.nih.gov/pubmed/37920508
http://dx.doi.org/10.1016/j.heliyon.2023.e21010
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author Zhangdi, Hanjing
Geng, Xinyu
Li, Ning
Xu, Ruiling
Hu, Ying
Liu, Jingyang
Zhang, Xu
Qi, Jihan
Tian, Yingying
Qiu, Jiawei
Huang, Shiling
Cang, Xueyu
Jin, Shizhu
author_facet Zhangdi, Hanjing
Geng, Xinyu
Li, Ning
Xu, Ruiling
Hu, Ying
Liu, Jingyang
Zhang, Xu
Qi, Jihan
Tian, Yingying
Qiu, Jiawei
Huang, Shiling
Cang, Xueyu
Jin, Shizhu
author_sort Zhangdi, Hanjing
collection PubMed
description Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis and found a significantly upregulated gene, Fstl1, in liver cirrhosis. In vivo and in vitro experiments showed that compared with those in the disease model group, the mRNA, and protein expression levels of Fstl1 were significantly reduced after BMSCs treatment, and the β-Catenin protein level was also significantly reduced after BMSCs treatment. Subsequently, we downregulated Fstl1 in activated hepatic stellate cells (HSCs) and found that Wnt and β-Catenin protein expression levels also decreased. Finally, we found that in BMSCs-treated activated HSCs, overexpression of Fstl1 reversed the inhibitory effect of BMSCs on the Wnt/β-Catenin signaling pathway to a certain extent. In summary, our results show that BMSCs can inhibit Wnt/β-Catenin signaling pathway activation by downregulating the protein expression level of Fstl1, thus alleviating cirrhosis. Therefore, targeted regulation of Fstl1 may provide a new therapeutic strategy for the progression of liver cirrhosis.
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spelling pubmed-106187712023-11-02 BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway Zhangdi, Hanjing Geng, Xinyu Li, Ning Xu, Ruiling Hu, Ying Liu, Jingyang Zhang, Xu Qi, Jihan Tian, Yingying Qiu, Jiawei Huang, Shiling Cang, Xueyu Jin, Shizhu Heliyon Research Article Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis and found a significantly upregulated gene, Fstl1, in liver cirrhosis. In vivo and in vitro experiments showed that compared with those in the disease model group, the mRNA, and protein expression levels of Fstl1 were significantly reduced after BMSCs treatment, and the β-Catenin protein level was also significantly reduced after BMSCs treatment. Subsequently, we downregulated Fstl1 in activated hepatic stellate cells (HSCs) and found that Wnt and β-Catenin protein expression levels also decreased. Finally, we found that in BMSCs-treated activated HSCs, overexpression of Fstl1 reversed the inhibitory effect of BMSCs on the Wnt/β-Catenin signaling pathway to a certain extent. In summary, our results show that BMSCs can inhibit Wnt/β-Catenin signaling pathway activation by downregulating the protein expression level of Fstl1, thus alleviating cirrhosis. Therefore, targeted regulation of Fstl1 may provide a new therapeutic strategy for the progression of liver cirrhosis. Elsevier 2023-10-20 /pmc/articles/PMC10618771/ /pubmed/37920508 http://dx.doi.org/10.1016/j.heliyon.2023.e21010 Text en © 2023 Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Zhangdi, Hanjing
Geng, Xinyu
Li, Ning
Xu, Ruiling
Hu, Ying
Liu, Jingyang
Zhang, Xu
Qi, Jihan
Tian, Yingying
Qiu, Jiawei
Huang, Shiling
Cang, Xueyu
Jin, Shizhu
BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway
title BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway
title_full BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway
title_fullStr BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway
title_full_unstemmed BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway
title_short BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway
title_sort bmscs alleviate liver cirrhosis by regulating fstl1/wnt/β-catenin signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618771/
https://www.ncbi.nlm.nih.gov/pubmed/37920508
http://dx.doi.org/10.1016/j.heliyon.2023.e21010
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