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. 2019 Apr 16;39(9):e00391-18. doi: 10.1128/MCB.00391-18

FIG 2.

FIG 2

HSP70 deficiency increases apoptotic priming and potential elimination of DNA-damaged hepatocytes and exerts differential effects on inflammatory and growth factor responses induced by carcinogen challenge. (A and B) Ki67 and TUNEL staining of liver or tumor (T) sections from WT or hsp70−/− mice at the indicated time points after DEN administration at P14. Quantification of Ki67+ proliferating cells or TUNEL+ apoptotic hepatocytes per high-power field (HPF) is presented (right panels). Original magnifications, ×200 (Ki67) and ×400 (TUNEL). Bars show mean ± standard error of the mean (SEM) (n = 4 or 5 mice per group). (C) Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. ALT and AST levels and ALT/AST ratio are shown for WT or hsp70−/− mice 8 months after DEN treatment (three right panels). Co., WT or hsp70−/− mice without DEN treatment served as controls. Bars show mean ± SEM (n = 5 mice per group). (D) Quantitative PCR of mRNA transcript levels of selected cytokines and growth factors in livers of DEN-treated mice. Bars represent mean ± SD (n = 4 or 5 mice). (E) Left, insignificant effect on hepatic LPS-induced signaling events in hsp70−/− mice. Representative WB analysis of IkBα degradation and levels of phosphorylated JNK1/2, STAT1, STAT3, and ERK in livers of WT and hsp70−/− mice are shown for the indicated time points after LPS injection (i.p. at 2.5 mg/kg of body weight) (from two experiments). Right, qPCR analysis of mRNA levels of inflammatory cytokines induced in response to LPS in the livers. Bars show mean ± SEM (n = 5 mice per group). (F) Effects of HSP70 ablation on DEN-induced MAPK signaling activation. Representative WB analyses of p-JNK1/2 (Y183/Y185), p-c-JUN (S63), and p-p38 (Y180/Y182) protein levels in the livers of WT and hsp70−/− mice at the indicated times post-DEN challenge are shown (from two experiments). For all panels, statistical significance is indicated (*, P < 0.05; **, P < 0.01; ***, P < 0.001). Bars indicate WT (filled) or hsp70−/− (open) mice.