Exploring effect of MANF in cholestatic liver injury in mice induced by rifampicin
- VernacularTitle:中脑星形胶质细胞神经营养因子在利福平诱导的小鼠胆汁淤积性肝损伤中的作用
- Author:
Shi-Guo CAO
1
;
Meng-Xue HUANG
;
Liu-Fang QU
;
Yang LI
;
Jiang-Long HONG
;
Gang CHEN
;
Wei-Ping ZHANG
Author Information
- Keywords: rifampicin; drug induced liver injury; a-daptive response,mesencephalic astrocyte-derived neurotrophic factor; gene knockout; bile acid trans-porter
- From: Chinese Pharmacological Bulletin 2024;40(8):1546-1551
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the involvement of mesencephalic astrocyte-derived neurotrophic factor(MANF)in rifampicin(RFP)-induced cholestatic liv-er injury.Methods We investigated the impact of MANF gene deletion on rifampicin-induced BAT ex-pression in mice by the MANF gene knockout mouse model.We investigated the influence of MANF knock-down on nuclear factor erythroid 2-related factor 2(Nrf2)in HepG2 cells by the MANF knockdown cell model.Results Compared with the wild-type(WT)mice,the mRNA and protein expression levels of bile salt export pump(BSEP)and multidrug-resistant asso-ciated protein4(MRP4)significantly increased in WT mice treated with RFP.However,compared to the WT mice treated with RFP,the mRNA and protein expres-sion levels of BSEP,Multidrug resistance protein 1(MDR1),multidrug resistance associated proteins 2/3/4(MRP2/3/4),and organic solute transport pro-teins α(OST α)were significantly reduced.In cell experiments we found that MANF knockdown weakened the expression of Nrf2 and its nuclear translocation by RFP.Conclusion MANF may regulate adaptive BAT expression by modulating Nrf2 expression,thereby pla-ying a protective role in RFP-induced liver injury.
