Transforming growth factor-ß signaling confers hepatic stellate cells progenitor features after partial hepatectomy.
J Cell Physiol
; 235(3): 2655-2667, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31584200
ABSTRACT
Liver regeneration involves not only hepatocyte replication but progenitor aggregation and scarring. Partial hepatectomy (PH), an established model for liver regeneration, reactivates transforming growth factor-ß (TGF-ß) signaling. Hepatic stellate cells (HSCs) are primarily responding cells for TGF-ß and resident in stem cell niche. In the current study, PH mice were treated with SB-431542, an inhibitor of TGF-ß Type I receptor, aiming to address the role of TGF-ß signaling on the fate determination of HSCs during liver regeneration. After PH, control mice exhibited HSCs activation, progenitor cells accumulation, and a fraction of HSCs acquired the phenotype of hepatocyte or cholangiocyte. Blocking TGF-ß signaling delayed proliferation, impaired progenitor response, and scarring repair. In SB-431542 group, merely no HSCs were found coexpressed progenitor makers, such as SOX9 and AFP. Inhibition of TGF-ß pathway disturbed the epithelial-mesenchymal transitions and diminished the nuclear accumulation of ß-catenin as well as the expression of cytochrome P450 2E1 in HSC during liver regeneration. We identify a key role of TGF-ß signaling on promoting HSC transition, which subsequently becomes progenitor for generating liver epithelial cells after PH. This process might interact with an acknowledged stem cell function signaling, Wnt/ß-catenin.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Hepatócitos
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Fator de Crescimento Transformador beta1
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Células Estreladas do Fígado
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Regeneração Hepática
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article