Figure 5.
ER stress and sensitivity to PI of κF-DH PCs. (A) MA plots of normalized transcript values from κF-DH vs WT (top) and κF-DH vs DH (bottom) PCs (n = 3 mice of each strain). Overexpressed genes, common in both comparisons, from the REACTOME unfolded protein response (UPR) pathway are represented. (B) Significantly enriched pathways based on the C2 canonical pathways from the Molecular Signature Database (MSignDB v.6.2). Analysis was performed in the 180 upregulated genes in κF-DH vs both controls (WT and DH PCs). FDR q values of the overlaps are represented on the bar graphs. (C) GO biological process enrichment analysis. Enrichment was performed in the 180 upregulated genes in κF-DH vs both controls (WT and DH PCs). FDR q values of the overlaps are represented on the bar graphs. (D) Quantitative transcriptional analysis of ER stress markers Herpud1, Hspa5, Ddit3, and Xbp1s in sorted CD138+ PCs of κF-DH, DH, and WT mice. Increase of Herpud1, Hspa5, and Ddit3 but not Xbp1s in κF-DH transcripts corroborates the transcriptomic analysis (n = 4 mice of each group). (E) Comparison of the absolute number of splenic CD138+ PCs between PI-treated (T) mice and nontreated (NT) mice. Percentage of depletion for each group is indicated over the bars (n = 5-8 mice of each group in 3 independent experiments). Means ± standard error of the mean, and comparisons between 2 groups were calculated using the nonparametric Mann-Whitney test. *P < .05, **P < .01. mRNA, messenger RNA; ns, nonsignificant.