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Updated: Aug 27, 2025
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
HSF2BP protects against acute liver injury by regulating HSF2/HSP70/MAPK signaling in mice
Jianbin Bi1,2, Jia Zhang1,3, Mengyun Ke1
1National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
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.
Insights
Heat shock protein 2 binding protein (HSF2BP) protects against acute liver injury by upregulating heat shock protein 70 (HSP70) and inhibiting MAPK signaling. This finding identifies HSF2BP as a potential therapeutic target for liver diseases.
Area of Science:
- Hepatology
- Molecular Biology
- Cellular Stress Response
Background:
- Heat shock proteins (HSPs) depletion and protein misfolding contribute to hepatocyte death and impaired liver regeneration.
- The role of heat shock factor 2 binding protein (HSF2BP) in the heat shock response (HSR) and liver injury remains unclear.
Purpose of the Study:
- To elucidate the function of HSF2BP in HSR and acute liver injury.
- To investigate the therapeutic potential of HSF2BP in liver damage.
Main Methods:
- Utilized knockout (KO) and transgenic (TG) mouse models.
- Administered acetaminophen (APAP) or D-GalN/LPS to induce liver injury.
- Assessed hepatocyte death, inflammation, liver function, and survival rates.
- Analyzed the expression of HSF2, HSP70, and MAPK pathway components (Jnk1/2, P38).
- Employed HSP70 siRNA to investigate pathway interactions.
Main Results:
- HSF2BP expression increased post-APAP administration, correlating with HSP70 levels.
- HSF2BP mitigated hepatocyte death, inflammation, and improved liver function in injury models.
- HSF2BP overexpression enhanced survival rates in APAP-induced liver injury.
- HSF2BP upregulated HSF2 and HSP70, while inhibiting Jnk1/2 and P38 MAPK activation.
- HSP70 knockdown abolished HSF2BP's protective effects on the MAPK pathway.
Conclusions:
- HSF2BP acts as a protective factor against acute liver injury.
- The HSF2BP/HSP70/MAPK axis is critical in liver injury pathogenesis.
- HSF2BP represents a promising therapeutic target for liver injury.
