Adipose-derived mesenchymal stem cells inhibit hepatic stellate cells activation to alleviate liver fibrosis via Hippo pathway.
Animals
Hepatic Stellate Cells
/ metabolism
Mesenchymal Stem Cells
/ metabolism
Rats
Liver Cirrhosis
/ therapy
Mesenchymal Stem Cell Transplantation
/ methods
Protein Serine-Threonine Kinases
/ metabolism
Hippo Signaling Pathway
YAP-Signaling Proteins
/ metabolism
Male
Rats, Sprague-Dawley
Signal Transduction
Adipose Tissue
/ cytology
Transcriptional Coactivator with PDZ-Binding Motif Proteins
Transcription Factors
/ metabolism
Acyltransferases
Transforming Growth Factor beta1
/ metabolism
Hepatic stellate cells
Hippo Pathway
Liver fibrosis
Mesenchymal stem cells
Therapeutics
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
24 Oct 2024
24 Oct 2024
Historique:
received:
30
03
2024
accepted:
09
10
2024
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Liver fibrosis is a common pathological process of chronic liver disease, characterized by excessive deposition of extracellular matrix (ECM). Mesenchymal stem cells (MSCs) have been found to have potential therapy effect on liver fibrosis, but the mechanism involved was still unclear. The objective of this study is to investigate the therapeutic efficacy of adipose-derived mesenchymal stem cells (ADMSCs) on the treatment of liver fibrosis, with particular emphasis on elucidating the underlying mechanism of action through which ADMSCs inhibit the activation of hepatic stellate cells (HSCs). ADMSCs were isolated from adipose tissue and injected intravenously into hepatic fibrosis model of rats. The histopathological changes, liver function, collagen deposition, the expression of fibroin and Hippo pathway were evaluated. In vitro, ADMSCs were co-cultured with HSCs activated by transforming growth factor beta The results showed that after the transplantation of ADMSCs, the liver function of rats was improved, the degree of liver fibrosis and collagen deposition were reduced, and the Hippo signaling pathway was activated. In vitro, ADMSCs can effectively inhibit the proliferation and activation of HSCs induced by TGF-β ADMSCs inhibit HSCs activation by regulating YAP/TAZ, thereby promoting functional recovery after liver fibrosis. These findings lay a foundation for further investigation into the precise mechanism by which ADMSCs alleviate liver fibrosis.
Sections du résumé
BACKGROUND
BACKGROUND
Liver fibrosis is a common pathological process of chronic liver disease, characterized by excessive deposition of extracellular matrix (ECM). Mesenchymal stem cells (MSCs) have been found to have potential therapy effect on liver fibrosis, but the mechanism involved was still unclear. The objective of this study is to investigate the therapeutic efficacy of adipose-derived mesenchymal stem cells (ADMSCs) on the treatment of liver fibrosis, with particular emphasis on elucidating the underlying mechanism of action through which ADMSCs inhibit the activation of hepatic stellate cells (HSCs).
METHODS
METHODS
ADMSCs were isolated from adipose tissue and injected intravenously into hepatic fibrosis model of rats. The histopathological changes, liver function, collagen deposition, the expression of fibroin and Hippo pathway were evaluated. In vitro, ADMSCs were co-cultured with HSCs activated by transforming growth factor beta
RESULTS
RESULTS
The results showed that after the transplantation of ADMSCs, the liver function of rats was improved, the degree of liver fibrosis and collagen deposition were reduced, and the Hippo signaling pathway was activated. In vitro, ADMSCs can effectively inhibit the proliferation and activation of HSCs induced by TGF-β
CONCLUSIONS
CONCLUSIONS
ADMSCs inhibit HSCs activation by regulating YAP/TAZ, thereby promoting functional recovery after liver fibrosis. These findings lay a foundation for further investigation into the precise mechanism by which ADMSCs alleviate liver fibrosis.
Identifiants
pubmed: 39449061
doi: 10.1186/s13287-024-03988-7
pii: 10.1186/s13287-024-03988-7
doi:
Substances chimiques
Yap1 protein, rat
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
YAP-Signaling Proteins
0
Transcriptional Coactivator with PDZ-Binding Motif Proteins
0
Transcription Factors
0
WWTR1 protein, rat
0
Tafazzin protein, rat
EC 2.3.1.-
Acyltransferases
EC 2.3.-
Transforming Growth Factor beta1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
378Subventions
Organisme : National Natural Science Foundation of China
ID : No. 32002353
Organisme : Natural Science Foundation of Sichuan Province
ID : No. 2022NSFSC1680
Informations de copyright
© 2024. The Author(s).
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