Fig. 4: Ent suppresses CAF activation and TGF-β- and TNF-α-induced responses.

a, b RT-qPCR data showing the expression of representative functional genes after 2 d Ent treatment (10 μM) in mouse (m) (imCAF1, a) and human (h) CAF (ONO, b) cells. c Scatter plot from RNA-seq data showing genes significantly upregulated (red, 2080) or downregulated (blue, 2502) by Ent (10 μM, 2 d) in ONO with functional genes highlighted. FDR q < 0.05. d Selected ontology terms enriched in the top 500 Ent-downregulated or -upregulated genes. e GSEA plots showing the enrichment of TGF-β and TNF-α pathway components in Ent-downregulated genes. f Dot plots showing the TGF-β (1 ng/ml, 2 d) induced expression changes under Veh or Ent treatment (10 μM, 2 d) at TGF-β-upregulated (333) or -downregulated (170) genes in ONO. g Heatmap from hierarchical clustering showing the expression changes by TGF-β, Ent or both at genes induced by TGF-β and sensitive to Ent-directed suppression. h Representative ontology terms enriched in the gene set in g. i RT-qPCR results confirming the Ent effect on selected TGF-β-induced genes in ONO. j Dot plots showing the TNF-α (10 ng/ml, 8 h) induced expression changes under Veh or Ent treatment (10 μM, 40 h pre-treatment plus 8 h concurrent treatment with TNF-α) at TNF-α-upregulated (398) or -downregulated (189) genes in hCAFs (YAM). k Heatmap showing the expression changes under the treatments of TNF-α, Ent or both at genes upregulated by TNF-α and sensitive to Ent-directed suppression. l Representative ontology terms enriched in the gene set in k. m RT-qPCR results confirming the Ent effect on selected TNF-α-induced genes in YAM. RT-qPCR (a, b, i, m), n = 3 independent samples; data are presented as mean values ± SEM. RNA-seq, n = 2 (ONO) and 3 (YAM) independent samples. Dot plots (f, j): bars, medians. *p < 0.05; **p < 0.01; ***p < 0.001. Two-sided t-test. GO analysis (d, h, l), one-sided Fisher’s exact test. Source data including p-values are provided as a Source Data file.