Figure 6
From: Acid Sphingomyelinase Inhibition Prevents Development of Sepsis Sequelae in the Murine Liver
Pharmacological inhibition of SMPD1 results in reduced HSC activation and reduced hepatic fibrosis. In long-term survivors (28 days following sepsis induction) (A) representative Sirius Red stainings, (B) hepatic fibrosis scores and Tgfb expression (Fig. 6A/B; n = 4 smpd1+/+, n ≥ 5 p-smpd1+/+, t-smpd1+/+) and (C) hepatic gene expression of fibrosis-associated genes (Fig. 6C; n = 4 smpd1+/+, n = 8 p-smpd1+/+, t-smpd1+/+) were determined. Transcriptional expression is normalized to reference gene (Actb) and shown as log2 fold changes. (D) Furthermore, stimulation for 24 hours with different desipramine concentrations (5 µM, 10 µM, 20 µM) of LX-2 cells were performed presenting dose dependent inhibition of ACTA2 as well as COL1A1 expression rate (Fig. 6D; n = 4). Transcriptional expression is normalized to reference genes (GAPDH) and presented in log2 fold changes. Cut off values were set at ± 1, representing a variation of biological significance (dotted lines). #p < 0.05; ##p < 0.01 vs. corresponding smpd1+/+ control; *p < 0.05; * *p < 0.01 vs. baseline (MWU-test).
