NUMB endocytic adaptor protein (NUMB) mediates the anti-hepatic fibrosis effect of artesunate (ART) by inducing senescence in hepatic stellate cells (HSCs).
10.1016/S1875-5364(25)60836-3
- Author:
Yangling QIU
1
;
Yujia LI
1
;
Mengran LI
1
;
Yingqian WANG
1
;
Min SHEN
2
;
Jiangjuan SHAO
1
;
Feng ZHANG
1
;
Xuefen XU
1
;
Feixia WANG
1
;
Zili ZHANG
3
,
4
;
Shizhong ZHENG
4
,
5
Author Information
1. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
2. Department of Biochemistry and Molecular Biology, Medical College, Yangzhou University, Yangzhou 225009, China.
3. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: njucm_zzl@
4. com.
5. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: nytws@
- Publication Type:Journal Article
- Keywords:
Artesunate;
Hepatic stellate cells;
Liver fibrosis;
NUMB endocytic adaptor protein;
Senescence;
Ubiquitylation
- MeSH:
Hepatic Stellate Cells/cytology*;
Liver Cirrhosis/genetics*;
Artesunate/pharmacology*;
Cellular Senescence/drug effects*;
Membrane Proteins/genetics*;
Animals;
Humans;
Nerve Tissue Proteins/genetics*;
Tumor Suppressor Protein p53/genetics*;
Male;
Mice
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(3):322-333
- CountryChina
- Language:English
-
Abstract:
Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
