2. Academic Validation
  3. Dihydroartemisinin requires NR1D1 mediated Rab7 ubiquitination to regulate hepatic stellate cells lipophagy in liver fibrosis

Dihydroartemisinin requires NR1D1 mediated Rab7 ubiquitination to regulate hepatic stellate cells lipophagy in liver fibrosis

  • Int J Biol Macromol. 2025 Feb 15;305(Pt 1):141055. doi: 10.1016/j.ijbiomac.2025.141055.
Zhengyang Bao 1,  Min Xu 1,  Yifan Kan 1,  Xiaohan Guo 1,  Mengran Li 1,  Junrui Wang 1,  Ya Zhou 1,  Zili Zhang 1,  Jiangjuan Shao 1,  Feng Zhang 1,  Li Chen 2,  Shizhong Zheng 3,  Ji Xuan 4
Affiliations

Affiliations

  • 1 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 2 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: 300643@njucm.edu.cn.
  • 3 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: nytws@njucm.edu.cn.
  • 4 Department of Gastroenterology, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, 305 Zhongshan East Road, Xuanwu Avenue, Nanjing, Jiangsu 210002, China. Electronic address: helio0009@126.com.
PMID: 39956231 DOI: 10.1016/j.ijbiomac.2025.141055
Abstract

The activation of hepatic stellate cells (HSCs) is a core event in the pathogenesis of liver fibrosis, typically accompanied by the disappearance of lipid droplets (LDs). Reversing the disappearance of HSCs LDs is a strategy to inhibit HSCs activation and alleviate liver fibrosis. Previous studies have shown that nuclear receptor subfamily 1 group d member 1 (NR1D1), as an important component of the biological clock system, is closely related to lipid metabolism. Our previous evidence indicated that Dihydroartemisinin (DHA) can regulate the lipid droplet metabolism of activated HSCs. Moreover, in CCl4 induced liver fibrosis mice, the liver clock gene NR1D1 is dysregulated. On this basis we explored the potential molecular mechanism of DHA inhibiting liver fibrosis through NR1D1. We found that DHA can inhibit liver fibrosis by restoring activated LDs of HSCs through inhibiting HSCs lipophagy. In summary, our study emphasizes the importance of NR1D1 in liver fibrosis and the potential of DHA to regulate NR1D1 in the treatment of liver fibrosis, providing a new direction for the treatment of liver fibrosis.

Keywords

Hepatic stellate cells; Lipophagy; NR1D1.

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