Neither hepatic IRE1α ablation nor pharmacological blocking of IRE1α activity has impacts upon the homeostasis or chemo-induced damage of the liver. (A–C)flox/flox (littermates) and LKO mice were i.p. injected with three doses of Vehicle (Veh.) and DOX (5 mg per kg body weight) at the time points shown in Fig. 2 B. (A) Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the mice. flox/flox+Veh., n = 6; LKO+Veh., n = 6; flox/flox+DOX, n = 6; LKO+DOX, n = 6. (B) Representative H&E (scale bar, 100 μm) and TUNEL (scale bar, 50 μm) staining of liver sections. (C) mRNA levels of Il6, Il1β, and Tnfα genes in the liver samples. flox/flox+Veh., n = 3; LKO+Veh., n = 3; flox/flox+DOX, n = 3; LKO+DOX, n = 3. (D–F)flox/flox (littermates) and LKO mice were i.p. injected with three doses of Vehicle and Cis (5 mg per kg body weight) at the time points shown in Fig. 2 E. (D) Serum AST and ALT of the mice. flox/flox+Veh., n = 6; LKO+Veh., n = 6; flox/flox+ Cis, n = 6; LKO+ Cis, n = 6. (E) Representative H&E (scale bar, 100 μm) and TUNEL (scale bar, 50 μm) staining of liver sections. (F) mRNA levels of Il6, Il1b, and Tnfa in the liver samples. flox/flox+Veh., n = 3; LKO+Veh., n = 3; flox/flox+DOX, n = 3; LKO+DOX, n = 3. (G–I) C57BL/6 male mice were i.p. injected with Vehicle, 4μ8C (3.3 mg per kg body weight, i.p.), DOX (5 mg per kg body weight, i.p.), or the combination of DOX and 4μ8C for three doses at the time points as indicated in Fig. 5 G. (G) Serum AST and ALT of the mice. Veh., n = 6; 4μ8C, n = 6; DOX, n = 6; DOX+4μ8C, n = 6. (H) Representative H&E (scale bar, 100 μm) and TUNEL (scale bar, 50 μm) staining of the liver sections. (I) mRNA levels of Il6, Il1b, and Tnfa in the liver samples. Veh., n = 3; 4μ8C, n = 3; DOX, n = 3; DOX+4μ8C, n = 3. (J–L) C57BL/6 male mice were i.p. injected with Vehicle, 4μ8C (3.3 mg per kg body weight), Cis (5 mg per kg body weight), or the combination of Cis and 4μ8C for three doses at the time points as indicated in Fig. 5 M. (J) Serum AST and ALT of the mice. Veh., n = 6; 4μ8C, n = 6; Cis, n = 6; Cis +4μ8C, n = 6. (K) Representative H&E (scale bar, 100 μm) and TUNEL (scale bar, 50 μm) staining of the liver sections. (L) mRNA levels of Il6, Il1b, and Tnfa in the liver samples. Veh., n = 3; 4μ8C, n = 3; Cis, n = 3; Cis+4μ8C, n = 3. Data are representative of two independent experiments and presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by two-way ANOVA (A, C, D, F, G, I, J, and L).
Figure S3.

Neither hepatic IRE1α ablation nor pharmacological blocking of IRE1α activity has impacts upon the homeostasis or chemo-induced damage of the liver. (A–C) flox/flox (littermates) and LKO mice were i.p. injected with three doses of Vehicle (Veh.) and DOX (5 mg per kg body weight) at the time points shown in Fig. 2 B. (A) Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the mice. flox/flox+Veh., n = 6; LKO+Veh., n = 6; flox/flox+DOX, n = 6; LKO+DOX, n = 6. (B) Representative H&E (scale bar, 100 μm) and TUNEL (scale bar, 50 μm) staining of liver sections. (C) mRNA levels of Il6, Il1β, and Tnfα genes in the liver samples. flox/flox+Veh., n = 3; LKO+Veh., n = 3; flox/flox+DOX, n = 3; LKO+DOX, n = 3. (D–F)flox/flox (littermates) and LKO mice were i.p. injected with three doses of Vehicle and Cis (5 mg per kg body weight) at the time points shown in Fig. 2 E. (D) Serum AST and ALT of the mice. flox/flox+Veh., n = 6; LKO+Veh., n = 6; flox/flox+ Cis, n = 6; LKO+ Cis, n = 6. (E) Representative H&E (scale bar, 100 μm) and TUNEL (scale bar, 50 μm) staining of liver sections. (F) mRNA levels of Il6, Il1b, and Tnfa in the liver samples. flox/flox+Veh., n = 3; LKO+Veh., n = 3; flox/flox+DOX, n = 3; LKO+DOX, n = 3. (G–I) C57BL/6 male mice were i.p. injected with Vehicle, 4μ8C (3.3 mg per kg body weight, i.p.), DOX (5 mg per kg body weight, i.p.), or the combination of DOX and 4μ8C for three doses at the time points as indicated in Fig. 5 G. (G) Serum AST and ALT of the mice. Veh., n = 6; 4μ8C, n = 6; DOX, n = 6; DOX+4μ8C, n = 6. (H) Representative H&E (scale bar, 100 μm) and TUNEL (scale bar, 50 μm) staining of the liver sections. (I) mRNA levels of Il6, Il1b, and Tnfa in the liver samples. Veh., n = 3; 4μ8C, n = 3; DOX, n = 3; DOX+4μ8C, n = 3. (J–L) C57BL/6 male mice were i.p. injected with Vehicle, 4μ8C (3.3 mg per kg body weight), Cis (5 mg per kg body weight), or the combination of Cis and 4μ8C for three doses at the time points as indicated in Fig. 5 M. (J) Serum AST and ALT of the mice. Veh., n = 6; 4μ8C, n = 6; Cis, n = 6; Cis +4μ8C, n = 6. (K) Representative H&E (scale bar, 100 μm) and TUNEL (scale bar, 50 μm) staining of the liver sections. (L) mRNA levels of Il6, Il1b, and Tnfa in the liver samples. Veh., n = 3; 4μ8C, n = 3; Cis, n = 3; Cis+4μ8C, n = 3. Data are representative of two independent experiments and presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by two-way ANOVA (A, C, D, F, G, I, J, and L).

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