肝损伤
热休克蛋白70
肝细胞
热休克蛋白
MAPK/ERK通路
p38丝裂原活化蛋白激酶
下调和上调
肝再生
药理学
发病机制
炎症
医学
信号转导
癌症研究
生物
化学
免疫学
细胞生物学
再生(生物学)
生物化学
体外
基因
作者
Jianbin Bi,Jia Zhang,Mengyun Ke,Tao Wang,Mengzhou Wang,Wuming Liu,Zhaoqing Du,Yifan Ren,Shuqun Zhang,Zheng Wu,Yi Lv,Rongqian Wu
标识
DOI:10.1038/s41419-022-05282-x
摘要
Abstract Heat shock proteins (HSPs) depletion and protein misfolding are important causes of hepatocyte death and liver regeneration disorder in liver injury. HSF2BP, as its name implies, is a binding protein of HSF2, but the specific role of HSF2BP in heat shock response (HSR) remains unknown. The aim of this study is to identify the role of HSF2BP in HSR and acute liver injury. In this study, we found that HSF2BP expression increased significantly within 24 h after APAP administration, and the trend was highly consistent with that of HSP70. hsf2bp - KO and hsf2bp - TG mouse models demonstrated HSF2BP reduced hepatocyte death, ameliorated inflammation, and improved liver function in APAP- or D-GalN/LPS- induced liver injury. Meanwhile, a significant increase of the survival rate was observed in hsf2bp - TG mice after APAP administration. Further studies showed that HSF2BP upregulated the expression of HSF2 and HSP70 and inhibited the activation of Jnk1/2 and P38 MAPK. Additionally, HSP70 siRNA pretreatment abolished the effect of HSF2BP on the MAPK pathway in APAP-treated hepatocytes. The results reveal that HSF2BP is a protective factor in acute liver injury, and the HSF2BP/HSP70/MAPK regulatory axis is crucial for the pathogenesis of liver injury. HSF2BP is a potential therapeutic target for liver injury.
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