Diarrhea in lymphocytic colitis: ERK1/2-dependent ENaC dysregulation and claudin-4-, -5- and -8-related barrier defects. Homo sapiens

Background: Lymphocytic colitis (LC) causes watery diarrhea. This study aimed to identify the inherent pathomechanisms of epithelial transport and barrier dysfunction and regulatory inputs. Methods: 8 (4 LC samples and 4 unrelated control samples) biopsies of fresh sigmoid colon were analysed by paired end sequencing (Illumina High Seq 2500) Conclusions: ENaC-mediated Na+ malabsorption via ERK1/2 and epithelial barrier dysfunction from tight junction downregulation through claudin-4, -5, and -8 are mechanisms causing malabsorptive and leak flux diarrhea in LC resulting from the key effector cytokines TNFa and INFg. Overall design: Sigmoid colon mRNA profiles from 8 unrelated individuals (4 with LC, 4 as control) were generated using paired end sequencing with Illumina High Seq 2500