Therapeutic effects of myocardin-related transcription factor A (MRTF-A) knockout on experimental mice with nonalcoholic steatohepatitis induced by high-fat diet.
Hum Exp Toxicol
; 40(10): 1634-1645, 2021 Oct.
Article
em En
| MEDLINE
| ID: mdl-33779332
ABSTRACT
OBJECTIVE:
To explore the effects of myocardin-related transcription factor A (MRTF-A) knockout on mice with nonalcoholic steatohepatitis (NASH) induced by high-fat diet (HFD).METHODS:
Normal-fat diet (NFD) or HFD was fed to MRTF-A-knockout (MRTF-A-/-) and wild-type (WT) mice for 16 weeks. Liver histopathological status was observed using Hematoxylin and Eosin (HE) staining, Oil Red O staining, Sirius Red staining, and Immunohistochemical staining. The mRNA and protein levels in liver tissues were measured through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot.RESULTS:
Compared with WT + HFD group, mice in MRTF-A-/- + HFD group were decreased in body weight, blood glucose, plasma insulin, liver TG and NAFLD activity score (NAS), with liver function recovery. Besides, compared with HFD-fed WT mice, HFD-fed MRTF-A-/- mice were improved in hepatic fibrosis, accompanied by decreased collagen content (%) and down-regulated expressions of α-SMA, COL1A2, TGFß1, and SMAD3. In mice fed with HFD, the expression of MCP-1, CCR2, F4/80 and CD68 declined in liver tissues of MRTF-A-/- mice as compared with WT mice. Besides, in hepatic macrophages isolated from HFD-fed mice, the observed increased expression of TNF-α, IL-1ß, MCP-1, as well as decreased expression of CCR2. Compared with WT + HFD group, MRTF-A-/- + HFD group mice were decreased regarding NF-κB p65 in liver tissues.CONCLUSION:
MRTF-A knockout reduced macrophage infiltration, down-regulated NF-κB p65 expression, and ameliorated inflammation and fibrosis of liver tissues in mice, thereby becoming a potential therapeutic target for NASH treatment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transativadores
/
Hepatopatia Gordurosa não Alcoólica
Limite:
Animals
Idioma:
En
Revista:
Hum Exp Toxicol
Ano de publicação:
2021
Tipo de documento:
Article