Journal: Frontiers in Pharmacology
Article Title: Integrated transcriptomics identifies ER stress–associated apoptosis in post-resuscitation AKI and supports early Dl-3-n-butylphthalide–associated renoprotection in a porcine TCA model
doi: 10.3389/fphar.2026.1841271
Figure Lengend Snippet: PT pseudo-bulk pathway enrichment and PERK–ATF4–CHOP axis-gene signals (A) Hallmark GSEA dot plot from PT pseudo-bulk analysis highlights Unfolded Protein Response and Apoptosis among the significantly altered pathways in the Sham versus IRI_12 h contrast. Because the contrast direction is Sham versus IRI_12h, negative NES values indicate enrichment toward the IRI_12 h condition. (B) PT pseudo-bulk volcano plot shows extensive transcriptional remodeling, with ERS/UPR- and apoptosis-related genes represented among the significantly altered signals. (C) Heatmap of axis-gene logFC across key PT pseudo-bulk contrasts shows coordinated changes in core UPR mediators, including Hspa5, Eif2ak3/PERK, Atf4, Ddit3/CHOP, Ern1/Xbp1, and Atf6, together with apoptosis-related genes including Bax, Bak1, Casp3/8/9, and Bcl2l1. Stars indicate FDR <0.05. (D) Bar plots of representative PT pseudo-bulk axis genes show contrast-level changes in PERK–ATF4–CHOP branch components, UPR-related mediators, and apoptosis-related effectors, including Eif2ak3/PERK, Atf4, Ddit3/CHOP, Hspa5, Ern1, Xbp1, Bax, and Bcl2l1. Stars indicate FDR <0.05.
Article Snippet: Among these branches, PERK–ATF4–CHOP signaling can shift from adaptive proteostasis regulation toward pro-apoptotic signaling under severe or sustained stress.
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