Human umbilical cord-derived mesenchymal stromal cells alleviate liver cirrhosis through the Hippo/YAP/Id1 pathway and macrophage-dependent mechanism
Copyright © 2023. Published by Elsevier B.V..
BACKGROUND: Few effective anti-fibrotic therapies are currently available for liver cirrhosis. Mesenchymal stromal cells (MSCs) ameliorate liver fibrosis and contribute to liver regeneration after cirrhosis, attracting much attention as a potential therapeutic strategy for the disease. However, the underlying molecular mechanism of their therapeutic effect is still unclear. Here, we investigated the effect of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in treating liver cirrhosis and their underlying mechanisms.
METHODS: We used carbon tetrachloride (CCl4)-induced mice as liver cirrhosis models and treated them with hUC-MSCs via tail vein injection. We assessed the changes in liver function, inflammation, and fibrosis by histopathology and serum biochemistry and explored the mechanism of hUC-MSCs by RNA sequencing (RNA-seq) using liver tissues. In addition, we investigated the effects of hUC-MSCs on hepatic stellate cells (HSC) and macrophages by in vitro co-culture experiments.
RESULTS: We found that hUC-MSCs considerably improved liver function and attenuated liver inflammation and fibrosis in CCl4-injured mice. We also showed that these cells exerted therapeutic effects by regulating the Hippo/YAP/Id1 axis in vivo. Our in vitro experiments demonstrated that hUC-MSCs inhibit HSC activation by regulating the Hippo/YAP signaling pathway and targeting Id1. Moreover, hUC-MSCs also alleviated liver inflammation by promoting the transformation of macrophages to an anti-inflammatory phenotype.
CONCLUSIONS: Our study reveals that hUC-MSCs relieve liver cirrhosis in mice through the Hippo/YAP/Id1 pathway and macrophage-dependent mechanisms, providing a theoretical basis for the future use of these cells as a potential therapeutic strategy for patients with liver cirrhosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:123 |
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| Enthalten in: |
International immunopharmacology - 123(2023) vom: 25. Okt., Seite 110456 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yao, Lichao [VerfasserIn] |
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| Links: |
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| Themen: |
Hepatic stellate cells |
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| Anmerkungen: |
Date Completed 27.09.2023 Date Revised 27.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2023.110456 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a BACKGROUND: Few effective anti-fibrotic therapies are currently available for liver cirrhosis. Mesenchymal stromal cells (MSCs) ameliorate liver fibrosis and contribute to liver regeneration after cirrhosis, attracting much attention as a potential therapeutic strategy for the disease. However, the underlying molecular mechanism of their therapeutic effect is still unclear. Here, we investigated the effect of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in treating liver cirrhosis and their underlying mechanisms | ||
| 520 | |a METHODS: We used carbon tetrachloride (CCl4)-induced mice as liver cirrhosis models and treated them with hUC-MSCs via tail vein injection. We assessed the changes in liver function, inflammation, and fibrosis by histopathology and serum biochemistry and explored the mechanism of hUC-MSCs by RNA sequencing (RNA-seq) using liver tissues. In addition, we investigated the effects of hUC-MSCs on hepatic stellate cells (HSC) and macrophages by in vitro co-culture experiments | ||
| 520 | |a RESULTS: We found that hUC-MSCs considerably improved liver function and attenuated liver inflammation and fibrosis in CCl4-injured mice. We also showed that these cells exerted therapeutic effects by regulating the Hippo/YAP/Id1 axis in vivo. Our in vitro experiments demonstrated that hUC-MSCs inhibit HSC activation by regulating the Hippo/YAP signaling pathway and targeting Id1. Moreover, hUC-MSCs also alleviated liver inflammation by promoting the transformation of macrophages to an anti-inflammatory phenotype | ||
| 520 | |a CONCLUSIONS: Our study reveals that hUC-MSCs relieve liver cirrhosis in mice through the Hippo/YAP/Id1 pathway and macrophage-dependent mechanisms, providing a theoretical basis for the future use of these cells as a potential therapeutic strategy for patients with liver cirrhosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hepatic stellate cells | |
| 650 | 4 | |a Hippo/YAP | |
| 650 | 4 | |a Human umbilical cord-derived mesenchymal stromal cells | |
| 650 | 4 | |a Liver cirrhosis | |
| 650 | 4 | |a Macrophages | |
| 650 | 7 | |a YAP-Signaling Proteins |2 NLM | |
| 650 | 7 | |a Inhibitor of Differentiation Protein 1 |2 NLM | |
| 700 | 1 | |a Hu, Xue |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Mengqin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Pingji |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qiuling |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Zhiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Lun |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yingan |e verfasserin |4 aut | |
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