NUMB endocytic adaptor protein mediates the anti-hepatic fibrosis effect of artesunate by inducing senescence in hepatic stellate cells

Developing and finding effective medications and targets to treat hepatic fibrosis is the urgent job at hand. Our previous work substantiated the effectiveness of artesunate (ART) in mitigating liver fibrosis by eradicating hepatic stellate cells (HSCs). The underlying mechanism remains unclear despite these revelations. It is interesting to note that NUMB endocytic adaptor protein (NUMB) has important implications for the treatment of hepatic diseases, but current research focuses on liver regeneration and hepatoma carcinoma. The elusive function of NUMB in liver fibrosis, particularly its capacity to regulate HSCs, requires further exploration. Here, we endeavor to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. It was discerned that expression level of NUMB significantly diminished in activated HSCs in comparison to quiescent HSCs, demonstrating a negative correlation with the progression of liver fibrosis. Furthermore, ART induced senescence in activated HSCs through the NUMB/P53 axis. We identified NUMB as a pivotal regulator of senescence in activated HSCs and as a mediator of ART in regulating cell fate. This study investigates the specific target of ART in eradicating activated HSCs, providing both theoretical and experimental substantiation for treatment of liver fibrosis.