Survivin expression is essential for early activation of hepatic stellate cells and fibrosis progression in chronic liver injury.
Life Sci
; 287: 120119, 2021 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-34743004
ABSTRACT
AIM:
Hepatic fibrosis in injured liver is characterized by the activation of hepatic stellate cells (HSCs) from their quiescent state. Survivin (BIRC5) is one of the key genes that are upregulated during activation of HSCs but their role in HSC activation and fibrosis progression is unknown. Here, we have investigated the role of survivin protein in early fibrogenic activation of HSCs and fibrosis progression in chronic liver injury. MATERIALS &METHODS:
Primary quiescent HSCs were isolated from healthy mice liver through perfusion and cultured for fibrogenic activation. Survivin expression was suppressed by its pharmacological suppressant, YM155. We developed chronic liver injury induced fibrotic mice model through administrating repeated dose of CCl4 for 2 weeks and 4 weeks. Mice were pre-treated with YM155 a week before CCl4 administration till 2nd week of dosing and then discontinued. Hepatic parameters were characterized and underlying mechanisms were investigated. KEYFINDINGS:
Survivin expression gradually increased along with the expression of αSMA, collagen I activation maker in HSCs during their activation from quiescent state. Survivin suppression through YM155 downregulated αSMA, collagen I. Pre-treatment of YM155 in mice ceased the early activation of HSCs and onset of fibrosis in injured liver. However, discontinuation of YM155 initiated the activation of HSCs and fibrosis progression that shows survivin expression in HSCs is essential for their early activation and onset of liver fibrosis.SIGNIFICANCE:
Survivin expression induces with activation of HSCs and drives onset of liver fibrosis in injured liver. Targeting survivin protein in activated HSCs could be a potential anti-fibrotic therapeutic approach in chronic liver injury.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Progressão da Doença
/
Células Estreladas do Fígado
/
Doença Hepática Terminal
/
Survivina
/
Cirrose Hepática
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2021
Tipo de documento:
Article