Endothelin-3 controls growth of colonic epithelial cells by mediating epithelial-mesenchymal interaction

It has been repeatedly reported that endothelin-3 (ET-3) is expressed by gastrointestinal mesenchymes, and that paracrine signaling between ET-3 and its receptor plays an essential role in controlling differentiation of the enteric nervous system in the gut, especially in the colon. However it remains to be solved whether ET-3 plays a role in regulating the growth of gastrointestinal epithelial cells. We have previously reported culture systems for forestomach, glandular stomach and duodenal epithelial cells, but a system for colonic epithelial cells has not been established. In the present study, we examined optimal culture conditions for colonic epithelial cells, and examined whether ET-3 affects the growth of gastrointestinal epithelial cells, with special reference to colonic cells. We found that ET-3 dose-dependently and region-specifically stimulated their growth in primary culture: colonic epithelial cells were most responsive, followed by duodenal and glandular stomach epithelial cells. Reverse transcription-polymerase chain reaction analysis showed that ET-3 and a receptor for ET-3 were expressed by both colonic mesenchymes and epithelia, but the levels were much higher in mesenchymes than in epithelia. These results suggest that ET-3 plays an important role in the growth control of colonic epithelial cells, possibly by mediating epithelial-mesenchymal interactions.