Mucosal acidosis elicits a unique molecular signature in epithelia and intestinal tissue mediated by GPR31-induced CREB phosphorylation

Significance Tissue acidification is commonly associated with active inflammation, including within the intestinal mucosa. It remains unclear how such acidification impacts cellular function and adaptation to these changes within the tissue. In the present work, we utilized unbiased gene expression profiling to identify pathways elicited by extracellular acidification. Results from these studies identify a prominent role for cyclic AMP response element-binding protein signaling in the molding of gene expression in intestinal epithelia. This acidification-induced phenotype is translatable from in vitro cell culture systems to in vivo murine models and through to patients with active intestinal inflammation.