Tumor necrosis factor-inducible gene 6 protein ameliorates chronic liver damage by promoting autophagy formation in mice.
Exp Mol Med
; 49(9): e380, 2017 09 22.
Article
em En
| MEDLINE
| ID: mdl-28935975
ABSTRACT
Tumor necrosis factor-inducible gene 6 protein (TSG-6) has recently been shown to protect the liver from acute damage. However, the mechanism underlying the effect of TSG-6 on the liver remains unclear. Autophagy is a catabolic process that targets cell components to lysosomes for degradation, and its functions are reported to be dysregulated in liver diseases. Here we investigate whether TSG-6 promotes liver regeneration by inducing autophagic clearance in damaged livers. Mice fed a methionine choline-deficient diet supplemented with 0.1% ethionine (MCDE) for 2 weeks were injected with TSG-6 (the M+TSG-6 group) or saline (the M+V group) and fed with MCDE for 2 additional weeks. Histomorphological evidence of injury and increased levels of liver enzymes were evident in MCDE-treated mice, whereas these symptoms were ameliorated in the M+TSG-6 group. Livers from this group contained less active caspase-3 and more Ki67-positive hepatocytic cells than the M+V group. The autophagy markers ATG3, ATG7, LC3-II, LAMP2A and RAB7 were elevated in the M+TSG-6 group compared with those in the M+V group. Immunostaining for LC3 and RAB7 and electron microscopy analysis showed the accumulation of autophagy structures in the M+TSG-6 group. TSG-6 also blocked both tunicamycin- and palmitate-induced apoptosis of hepatocytes and increased their viability by inducing autophagy formation in these cells. An autophagy inhibitor suppressed TSG-6-mediated autophagy in the injured hepatocytes and livers of MCDE-treated mice. These results therefore demonstrate that TSG-6 protects hepatocytes from damage by enhancing autophagy influx and contributes to liver regeneration, suggesting that TSG-6 has therapeutic potential for the treatment of liver diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Moléculas de Adesão Celular
/
Hepatopatias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Exp Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
2017
Tipo de documento:
Article