Fig. 4: PPARδ promotes inflammation-related signaling pathways and KRAS^mu activation during pancreatic tumorigenesis.

a, b KC and KC/Pd mice at 6−8 weeks of age were fed the GW diet (50 mg/kg) for 3 days. The total RNA of pancreata from these mice was extracted for RNA-sequencing transcriptome profile analyses (n = 3−4 per group). a Heatmap of differentially expressed genes with P(Adj)<0.05 between the GW diet–treated KC (KC_GW) and KC/Pd (KC/Pd_GW) mouse groups. b Pathway enrichment results for KC/Pd_GW vs. KC_GW mice obtained by gene set enrichment analyses using R package “ClusterProfiler”, a cutoff of P(Adj)=0.05, and gene sets=MSigDB category “Hallmark gene sets”. The inflammation-related and KRAS signaling pathways are marked in a red square. c Il6 mRNA levels measured by qRT-PCR of pancreata from the KC and KC/Pd mice at 6–8 weeks of age fed the GW diet for 3 days, (n = 5–6 biologically independent samples). d–m Representative images of IHC staining for p-Stat3 (Tyr705) (d, e) and their quantitative results (f, g, n = 5 biologically independent samples), Western blot for p-Stat3 and p-Erk1/2 (h, i), and IHC staining for p-Erk1/2 (j, k) and their quantitative results (l, m, n = 5 biologically independent samples) for KC and KC/Pd mice on the GW diet for 0, 3, and 9 days as described in Fig. 3b (d, f, h, j, l) or on the HFD or Ctrl for 12 weeks as described in Fig. 2b (e, g, i, k, and m). Data are mean ± SEM. For (c), unpaired two-tailed Student’s t test, and for (f), (g), (l, m), two-way ANOVA with Bonferroni correction. ***P < .001, and ****P < .0001. Source data are provided as a Source Data file.