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. 2023 Jun 23;14:3761. doi: 10.1038/s41467-023-39291-x

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — A GSEA analysis of the UPR and ER stress gene sets down-regulated in Nfic^-/- pancreata and up-regulation of UPR. B, C RT-qPCR analysis of ER stress-related transcripts in WT and Nfic^-/- pancreata (n ≥ 6/group) (B) and in freshly isolated acini (n ≥ 3/group) (C). Two-tailed Mann–Whitney U-test was used to calculate statistical significance in B and C, except for BiP in C where two-tailed Student T-test was used (B Xbp1 spliced, P = 0.0038; BiP, P = 0.009; Chop, P = 0.008; Hsp90b1, P = 0.0101) (C Xbp1 spliced, P = 0.028; BiP, P = 0.005; Chop, P = 0.008; Hsd17b11, P = 0.028; Hsp90b, P = 0.01). D Western blotting showing up-regulation of BIP and CHOP in Nfic^-/- pancreata (n = 7/group) (two-tailed Mann–Whitney U-test; BiP, P = 0.0175; CHOP, P = 0.047). Bar graph with densitometric quantification of data. E IF analysis of BIP in wild type and Nfic^-/- pancreata (n ≥ 7/group). Boxplot shows quantification of the BIP expression intensity in WT and Nfic^-/- pancreata. Individual dots correspond to the average of at least 15 images for each pancreas, scale bar = 10 μm. F ChIP-qPCR showing binding of NFIC, but not NR5A2, to the promoters of Hspa5/Bip-1, Ddit3 and Hsp90aa1 (n = 4) (two-tailed Mann–Whitney U-test; BiP, Chop and Hsp90aa1, P = 0.0286 in the NFIC ChIP). G 266-6 cells incubated for 24 h or 36 h with vehicle or increasing TM concentrations (10 nM, 1 nM, 0.1 nM). Data shows the up-regulation of BIP and the down-regulation of NFIC by 24/36 h and the down-regulation of NR5A2 by 24 h in TM-treated cells (one of three independent experiments is shown). H Up-regulation of BIP and CHOP in 266-6 cells treated with TM upon Nfic knockdown. Boxplot shows quantification of data (n = 3 replicates/group) [two-tailed Student T-test; BiP in Nfic sh#1, P = 0.002; in Nfic sh #2, P = 0.004; in Nfic sh #3, P = 0.005. Chop in Nfic sh #1, P = 0.0038; in Nfic sh #2, P = 0.002; in Nfic sh #3, P = 0.001]. I Reduced BIP and CHOP expression in control and NFIC-overexpressing 266-6 cells treated with TM [two-tailed Student T-test; 24 h: BiP, P = 0.01; CHOP, P = 0.02; 36 h: BiP, P = 0.04; CHOP, P = 0.03]. Boxplots show quantification of data (n = 3 replicates/group). P < 0.1 (#), P < 0.05 (*), P < 0.01 (**); two-tailed Mann–Whitney U-test to calculate the significance in all panels. Boxplots show the minimum, the maximum, the sample median, and the first and third quartiles. Source data are provided as a Source Data file.