Extended Data Fig. 2: Deletion of Aldh1l2 in models of acinar-to-ductal metaplasia and acute pancreatitis.
From: ALDH1L2 regulates reactive oxygen species and acinar-to-ductal metaplasia in the pancreas
A) Level of blood glucose in WT and Aldh1l2 KO mice over time. B) Weight of WT and Aldh1l2 KO mice at 8 weeks (WT, n = 9; KO, n = 7) and 100 weeks (WT, n = 9; KO, n = 7). Data represented as mean ± SD and representative of two independent experiments. Unpaired t-test. C) Basal level of serum amylase in WT (n = 10) and Aldh1l2 KO (n = 9) mice. Data represented as mean ± SD. Data representative of 2 independent experiments. Unpaired t test. D) Representative images of MDA staining quantified in Fig. 2b. E) Relative levels of oxidized glutathione (GSSG) in Aldh1L2 WT or KO pancreatic tissue as measured by LC-MS. Data represented as mean ± SD of the relative peak area of n = 7 mice for WT group and n = 6 for Aldh1l2 KO group. Representative of 2 independent experiments. Unpaired t test, *p-value = 0.0376 F) Ratio of GSH to GSSG measured in Aldh1l2 WT and KO pancreatic tissue. Data represented as mean ± SD of the relative peak area of n = 7 mice for WT group and n = 6 for Aldh1l2 KO group. Representative of 2 independent experiments. Unpaired t test. G) Relative levels of reduced glutathione (GSH) in Aldh1L2 WT or KO pancreatic tissue as measured by LC-MS. Data represented as mean ± SD of the relative peak area of n = 8 mice for WT group and n = 6 for Aldh1l2 KO group. Representative of 2 independent experiments. Unpaired t test. H) ALDH1L2 and CK19 protein expression in ex-vivo culture of Aldh1l2 WT and KO acinar cells undergoing ADM. Representative of 2 independent experiments. I) Representative images of 3D acinar cell cultures embedded in collagen undergoing ADM. J) Proportion of ductal structures bigger or smaller than 100 μm of Aldh1l2 WT acinar cells after 4 days of culture with or without 300μM NAC. Data represented as a proportion of total of n = 139 for untreated and n = 126 for NAC-treated. Chi-square test. K) Scheme of acute pancreatitis protocol. WT or Aldh1l2 KO mice received 6 intraperitoneal injections of either PBS or Caerulein, per day over two days. Serum for amylase quantification was collected at the end of the second day of injections. Mice were sacrificed at day 4 to assess acute pancreatitis severity. Created using BioRender L) Quantification of fibrosis by Picrosirius red staining of the pancreas of mice with acute pancreatitis at day 4. Data represented as mean ± SEM, Brown-Forsythe and Welch Anova test, * p-value = 0.0252. M) Quantification of ADM by immunohistochemistry at day 4 and day 7 of pancreatitis in WT (n = 5) and Aldh1l2 KO (n = 6) mice. Data represented as mean ± SD. Two-way anova, ****p-value < 0.0001, **p-value = 0.0024.
