2. Academic Validation
  3. Hsp47 acts as a bridge between NLRP3 inflammasome and hepatic stellate cells activation in arsenic-induced liver fibrosis

Hsp47 acts as a bridge between NLRP3 inflammasome and hepatic stellate cells activation in arsenic-induced liver fibrosis

  • Toxicol Lett. 2022 Nov 1;370:7-14. doi: 10.1016/j.toxlet.2022.07.816.
Weizhuo Yuan 1,  Tianming Qiu 2,  Xiaofeng Yao 3,  Chenbing Wu 4,  Yan Shi 5,  Ningning Wang 6,  Jingyuan Zhang 7,  Liping Jiang 8,  Xiaofang Liu 9,  Guang Yang 10,  Jie Bai 11,  Xiance Sun 12
Affiliations

Affiliations

  • 1 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: jmsywz@163.com.
  • 2 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: qtm1992@163.com.
  • 3 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: yaoxiaofeng@dmu.edu.cn.
  • 4 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: bb978192507@163.com.
  • 5 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: sy17865202084@163.com.
  • 6 Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: zkxwnn@dmu.edu.cn.
  • 7 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: 13704357701@163.com.
  • 8 Preventive Medicine Laboratory, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, 116044, PR China. Electronic address: dljlp@dmu.edu.cn.
  • 9 Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: food@dmu.edu.cn.
  • 10 Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China.
  • 11 Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China; Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: woshixiaobaige@163.com.
  • 12 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China; Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: sunxiance@dmu.edu.cn.
PMID: 35963424 DOI: 10.1016/j.toxlet.2022.07.816
Abstract

The activation of hepatic stellate cells (HSCs) is a key event during the progression of liver fibrosis (LF). We have previously indicated that NLRP3 inflammasome plays a crucial role in arsenic-induced HSCs activation. However, the mechanism of cascade responses between NLRP3 inflammasome and HSCs activation is unclear. Here, we showed that the transcription and protein level of Hsp47 was upregulated after 4 μM arsenic treatment, both in vivo and in vitro. Additionally, arsenic-induced HSCs activation was remarkably alleviated by the interference of Hsp47. Furthermore, blockage of NLRP3 significantly mitigated the activation of the NLRP3 inflammasome and decreased the expression of Hsp47, thereby attenuating the arsenic-induced HSCs activation. However, the ablation of Hsp47 did not affect the activation of the NLRP3 inflammasome. Notably, the protein-protein interaction between NLRP3 and Hsp47 was observed both in vivo and in vitro, and the target amino acid sequences were further identified. In summary, the present study indicated that NaAsO2 induced HSCs activation via the NLRP3 inflammasome-Hsp47 pathway. These findings provide direct evidence that Hsp47 may be a potential therapeutic target for arsenic-induced LF.

Keywords

Arsenic; Hepatic stellate cells; Hsp47; Liver fibrosis; NLRP3 inflammasome.

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