PTEN Overexpression Alters Autophagy Levels and Slows Sodium Arsenite-Induced Hepatic Stellate Cell Fibrosis

Abstract

Exposure to inorganic arsenic remains a global public health problem. The liver is the main target organ, leading to arsenic-induced liver fibrosis. Phosphatase and tensin homology deleted on chromosome ten (PTEN) may participate in arsenic-induced liver fibrosis by regulating autophagy, but the exact mechanisms remain unclear. We established a mouse model of arsenic poisoning through their drinking water and a fibrosis model using the human hepatic stellate cell line LX-2 through NaAsO2 exposure for 24 h. Masson staining measured liver fibrosis. The cells were transfected with a PTEN overexpression plasmid. Western blot and qRT-PCR determined the levels of protein/mRNA expression. Fibrosis was evident in both the mouse model and arsenic-exposed LX-2 cells. NaAsO2 upregulated expression of autophagic markers microtubule-associated protein light chain A/B (LC3), recombinant human autophagy effector protein (Beclin-1), and hairy and enhancer of split homolog-1 (HES1), but downregulated PTEN. Alongside this, α-smooth muscle actin (α-SMA) expression was significantly upregulated by NaAsO2. PTEN overexpression altered NaAsO2-induced autophagy and downregulated LC3 and Beclin-1. While Notch1, HES1, α-SMA, and collagen I expression were all downregulated in the NaAsO2 groups. Therefore, PTEN overexpression might decrease autophagy and inhibit fibrosis progression caused by arsenic, and the NOTCH1/HES1 pathway is likely involved.

SLC7A11 Silencing Modulates Ferroptosis and Autophagy to Reduce Sodium Arsenite-Induced Activation of Hepatic Stellate Cells

“…Furthermore, Meng D [43] noted that carvedilol mitigates liver fibrosis by inhibiting autophagy and promoting apoptosis in HSCs. Previous research by our group has revealed that inorganic arsenic can induce autophagy, thereby promoting liver fibrosis [44]. Recent studies suggest that SLC7A11 may be involved in the autophagy process.…”