Transcriptional Regulation of SLC26A3 (DRA) by CDX2

• DOI: 10.1096/fasebj.31.1_supplement.1049.10
• Publication Date: 2023-11-26T17:01:18Z
• Authors: Ishita Chatterjee; Anoop Kumar; Rosa Mª Castilla ...; Oscar Pellon‐Card...; Alip Borthakur; Ravinder Gill; Waddah Alrefai; Michael Verzi; Pradeep Kumar Dudeja
• Keywords: CDX2; Villin

Background SLC26A3 (Down Regulated in Adenoma, DRA) plays a key role mammalian intestinal NaCl absorption via mediating apical membrane Cl − /HCO 3 exchange. DRA function and expression is significantly decreased diarrheal diseases associated with infections inflammatory bowel (IBD). Since, now being touted as an important therapeutic target for infectious IBD diarrhea, it critical to understand the detailed mechanisms of regulation at molecular cellular level health disease. Earlier studies showed that, epithelial caudal‐related homeobox transcription factor 2 (CDX2) essential regulator homeostasis also involved differentiation. Interestingly, higher differentiated cells silico analysis promoter consensus sites CDX2 binding. Aim Current were, therefore, undertaken test hypothesis that regulates transcription. Methods Cdx2 Fl/Fl ;Villin‐CreERT2 mice, [where tamoxifen (TAM) deletes intestine], were used these Caco2 vitro model study overexpression silencing effects by transfecting cDNA siRNA, respectively. mRNA protein levels assessed real time RT‐PCR immunoblotting/immuno‐staining, activity was determined luciferase assay. Direct binding region chromatin immuno‐precipitation (CHIP) electrophoretic mobility shift assay (EMSA). Results /− mice marked reduction ileum (Arbitrary units: WT=2.73 ± 1.04, KO=0.029 0.02 (P<0.05), proximal colon (PC) WT=1.87 0.53, KO=0.51 0.08; P <0.05) distal (DC) (WT=1.75 0.46, KO=0.02 ±0.02, P<0.05) well compared wild type mice. Similarly, resulted (~ 50%) decrease levels, whereas, ectopic over‐expression up‐regulated expression. stimulated ~10‐fold, indicating its transcriptional regulation. We next utilized EMSA ChIP assays demonstrate direct one putative cis elements identified 645 663 (+) promoter. Conclusion Our studies, first time, CDX2. Given has been shown be downregulated UC (ulcerative colitis) CD (crohn's disease) patients, may least partly responsible observed IBD. Support or Funding Information Supported NIDDK/Department Veteran Affairs