Taurine attenuates activation of hepatic stellate cells by inhibiting autophagy and inducing ferroptosis

Figure 1 Effects of taurine on extracellular matrix. A: Detection of effect of taurine on the viability of hepatic stellate cells by Cell Counting Kit-8 method; B: Detection of the effect of taurine on mRNA expression of fibronectin 1, collagen I, and α-SMA by reverse transcription-polymerase chain reaction; C: Detection of effect of taurine on protein expression of fibronectin 1, collagen Ι, and α-SMA by Western blot. Data are expressed as the mean ± SD. ^aP < 0.05 vs control, ^bP < 0.01 vs control, ^cP < 0.05 vs platelet-derived growth factor-BB (PDGF-BB), ^dP < 0.01 vs PDGF-BB. PDGF-BB: Platelet-derived growth factor-BB.

Figure 2 Taurine inhibits autophagy in hepatic stellate cells. A: Effect of taurine on expression of autophagy-related molecules; B: Taurine decreases the number of autophagosomes. Yellow arrows indicate monolayer or bilayer autophagosomes. Bar = 1 μm. Data are expressed as the mean ± SD. ^aP < 0.05 vs control, ^bP < 0.01 vs control, ^cP < 0.05 vs platelet-derived growth factor-BB (PDGF-BB), ^dP < 0.01 vs PDGF-BB. PDGF-BB: Platelet-derived growth factor-BB.

Figure 3 Taurine induces ferroptosis in hepatic stellate cells. A: Effect of taurine on expression of ferroptosis-related molecules; B: Effect of taurine on levels of glutathione and malondialdehyde; C: Effect of taurine on reactive oxygen species; D: Effect of taurine on mitochondrial structure of hepatic stellate cells. Red arrows indicate mitochondria. Bar = 1 μm; E: Taurine induces iron deposition in hepatic stellate cell. Data are expressed as the mean ± SD. ^aP < 0.05 vs control, ^bP < 0.01 vs control, ^cP < 0.05 vs platelet-derived growth factor-BB (PDGF-BB), ^dP < 0.01 vs PDGF-BB. PDGF-BB: Platelet-derived growth factor-BB; GSH: Glutathione; MDA: Malondialdehyde.

Figure 4 Molecular docking results of taurine and ferritin heavy chain 1 and nuclear receptor coactivator 4, respectively. FTH1: Ferritin heavy chain 1; NCOA4: Nuclear receptor coactivator 4.

Figure 5 Mechanisms associated with taurine-mediated death and inactivation of hepatic stellate cells in liver fibrosis. A: Inhibition of autophagy; B: Activation of ferritinophagy; C: Induction of ferroptosis. FTH1: Ferritin heavy chain 1; NCOA4: Nuclear receptor coactivator 4; ROS: Reactive oxygen species; HSC: Hepatic stellate cell; GSH: Glutathione.