Autophagic-CTSB-inflammasome axis modulates hepatic stellate cells activation in arsenic-induced liver fibrosis.

Long-term exposure to arsenic can cause liver injury and fibrosis. The activation of hepatic stellate cells (HSCs) plays an essential role in the process of liver fibrosis. We found that NaAsO2 caused liver damage and fibrosis in vivo, accompanied by excessive collagen deposition and HSCs activation. In addition, NaAsO2 upregulated autophagy flux, elevated the level of cytoplasmic cathepsin B (CTSB), and activated the NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome in a subtle way. Consistent with these findings in vivo, we demonstrated that NaAsO2-induced activation of HSCs depended on CTSB-mediated NLRP3 inflammasome activation in HSC-t6 cells and rats primary HSCs. Moreover, inhibition of autophagy decreased the cytoplasmic CTSB and alleviated the activation of the NLRP3 inflammasome, thereby attenuating the NaAsO2-induced HSCs activation. In summary, these results indicated that NaAsO2 induced HSCs activation via autophagic-CTSB-NLRP3 inflammasome pathway. These findings may provide a novel insight into the potential mechanism of NaAsO2-induced liver fibrosis.