Anion exchange regulates intestinal mucus expansion while Cftr regulates de novo mucus secretion

Abstract

The intestinal epithelium is covered by mucus that protects the tissue from the luminal content. Studies have shown that anion secretion via the cystic fibrosis conductance regulator (Cftr) regulates mucus formation in the small intestine. However, mechanisms regulating mucus formation in the colon are less understood. The aim of this study was to explore the role of anion transport in regulation of mucus formation during steady state, and in response to carbamylcholine (CCh) and prostaglandin E2 (PGE2). Cftr{Delta}F508 (CF) mice were used to assess the role of Cftr, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) was used to inhibit anion exchange. In the distal colon, steady state mucus expansion was reduced by apical DIDS, and normal in CF mice. PGE2 stimulated mucus expansion without de novo mucus secretion in wild type (WT) and CF distal colon via DIDS sensitive mechanisms, while CCh induced de novo mucus secretion in WT but not in CF colon. However, when added simultaneously, CCh and PGE2, stimulated de novo mucus secretion in CF colon via DIDS sensitive pathways. A similar response was observed in CF ileum that responded to CCh and PGE2 with DIDS sensitive de novo mucus secretion. In conclusion, this study suggests that apical anion exchange regulates intestinal mucus expansion, while Cftr regulates de novo mucus secretion from ileal and distal colon crypts. Furthermore, these findings demonstrate that in the absence of a functional Cftr channel, activation of anion exchange can help release mucus from intestinal goblet cells.