Fig. 3. Identification of PRKAB1 as a therapeutic target to promote intestinal barrier function.

A Computational workflow for identification of PRKAB1 as a druggable target for promoting a barrier-protective transcriptional program within the IBD network. B Schematic summarizing key components of the SPS-pathway used in fortifying tight junctions and promoting apical-basal polarity. C, D Detailed view of two prominent disease paths identifying downregulation of PRKAB1 as a shared early event in IBD pathogenesis [see a complete list of genes in Table 1]. E The expression of PRKAB1 and CLDN2 transcript levels (qPCR) was assessed in the ileum and colon biopsies of IBD patients (UC = 16 and CD = 14) or healthy controls (n = 8). The different locations of the tissue specimens from UC and CD subjects were shown in different colors, as stated in the figure. Data represented as mean ± S.E.M. and two-tailed Mann–Whitney test using p = 0.05 cutoff was used to calculate significance. F IHC of IBD patient colon biopsies assessed for expression of PRKAB1 and CLDN2. Representative images are shown [expanded selection of IHC in Supplementary Fig. S9]. G Activation status of SPS-pathway was analyzed in FFPE colon biopsies from UC/CD patients using an anti-pS²⁴⁵-GIV antibody. Representative images are shown. Scale bars = 100 µm. The method for assessing the SPS-pathway and details regarding the phospho-specific antibody is included in Supplementary Fig. S10. H Bar graphs showing the frequency of SPS pathway activation in healthy vs. IBD patients. Two-sided Fisher’s exact test was used to calculate significance. Source data are provided as a Source Data file.