Silencing of tissue factor by antisense deoxyoligonucleotide mitigates thioacetamide-induced liver injury.
Naunyn Schmiedebergs Arch Pharmacol
; 393(10): 1887-1898, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32430618
ABSTRACT
BACKGROUND:
Retinoid receptors (RRs), RAR-α and RXR-α, work as transcription factors that regulate cell growth, differentiation, survival, and death. Hepatic stellate cells (HSCs) store retinoid and release its RRs as lipid droplets upon their activation.PURPOSE:
We test the hypothesis that loss of retinoid receptors RAR-α and RXR-α from HSCs is dependent on tissue factor (TF) during thioacetamide (TAA)-induced liver injury.METHODS:
Liver toxicity markers, TF, fibrin, cleaved caspase-3, and cyclin D1 as well as histopathology were investigated.RESULTS:
Increased TF, fibrin, cleaved caspase-3, and cyclin D1 protein expression is seen in zone of central vein after TAA injection compared with vehicle-treated mice. A strong downregulation of RAR-α and RXR-α is seen in TAA-induced liver injury. In addition, histopathological obliteration and pericentral expression of cleaved caspase 3 and cyclin D1 are observed after TAA injection compared with the normal vehicle-treated mice. No changes have been seen in TAA/TF-sense (SC) in whole parameters compared with TAA-treated animals. TAA/TF-antisense (AS)-treated mice show normal expression of all parameters and normal histopathological features when compared with the control mice. In conclusion, this study declares that the strong downregulation of RAR-α and RXR-α may cause liver injury and particularly activation of HSCs in TAA-induced toxicity. TF-AS treatment not only downregulates TF protein expression but also alleviates loss of liver RAR-α and RXR-α and suppresses the activated apoptosis signals in TAA-induced liver toxicity. Finally, TF and RAR-α/RXR-α are important regulatory molecules in TAA induced acute liver injury.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tioacetamida
/
Tromboplastina
/
Oligonucleotídeos Antissenso
/
Doença Hepática Induzida por Substâncias e Drogas
Limite:
Animals
Idioma:
En
Revista:
Naunyn Schmiedebergs Arch Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Egito