Fig. 6: PPARδ alteration directly modulates chemokine CCL2 expression in mouse and human pancreatic epithelial cells. | Nature Communications

Fig. 6: PPARδ alteration directly modulates chemokine CCL2 expression in mouse and human pancreatic epithelial cells.

From: Rapid acceleration of KRAS-mutant pancreatic carcinogenesis via remodeling of tumor immune microenvironment by PPARδ

Fig. 6

a–c Pancreatic tissues from KC or KC/Pd mice fed the HFD or Ctrl diet; and KC/Pd mice fed the GW or Ctrl diet for 3 days (n = 3–4 biologically independent samples). Venn diagram of differentially expressed chemokines (a). Quantitative results of Ccl2 protein levels for KC/Pd mice on the GW diet (b) and KC or KC/Pd mice on the HFD (c). d Representative images of Ccl2 RNAscope in situ hybridization for normal pancreatic tissues of KC/Pd mice fed the GW or Ctrl diet for 3 days (n = 3 biologically independent samples). e Venn diagram of differentially expressed chemokines for mouse tdTomato RFP–sorted pancreatic epithelial cells of KC/tdPd mice on GW or control diet for 3 days and for the cell culture media from mouse NB490 KPC cells with WT or Ppard KO. f, g Quantitative results of Ccl2 protein levels for tdTomato-RFP+ cells (f, n = 4 biologically independent samples) and for the cell culture media from mouse NB490 KPC cells from 4 independent experiments (g). h, i Ccl2 mRNA expression levels in tdTomato-RFP+ pancreatic epithelial cells (h, n = 4 biologically independent samples) and in mouse NB490 KPC cells from 4 independent experiments (i). j Ccl2 mRNA expression levels in mouse KC and KC/Pd PDAC cells with or without GW treatment from 4 independent experiments. k, l PPARδ (k) and CCL2 (l) mRNA expression levels in human PDAC cells transfected with PPARδ siRNAs (siPPARD) or control siRNA (Ctrl) from 3 independent experiments. m The PPARδ binding to the four predicted PPARδ binding sites (pPDBS) in the mCcl2 promoter in mouse KC PDAC cells stably transduced with mouse DDK-tagged PPARδ expressing lentivirus and treated with 1 µM GW or solvent (DMSO) from 3 independent experiments. Data are mean ± SEM. For (b), (f), (h), unpaired two-tailed Student’s t test, for (c), (k–m), multiple t-tests, for (g), (i), one-way ANOVA with Bonferroni correction, and for (j), two-way ANOVA with Bonferroni correction. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Source data are provided as a Source Data file.

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