JNK pathway is required for CCK induced pancreatic growth in a model for regeneration

Pancreatic regeneration after pancreatitis involves dedifferentiation of acinar cells which display embryonic characteristics followed by replication and redifferentiation. Pancreatic acinar cell growth in culture is known to be stimulated by CCK but accompanied by dedifferentiation. We have now further characterized pancreatic growth in acinar cell monolayer culture on collagen and found that the reduced expression of digestive enzymes is accompanied by an increased expression of the embryonic markers β‐catenin and E‐cadherin at both protein and mRNA level. We used these undifferentiated cultured acinar cells to evaluate the signaling pathway activation involved in CCK action to stimulate acinar cell growth; [ 3 H] thymidine incorporation was used as a read out of DNA synthesis. Dominant negative JNK2 and dominant negative c‐jun (without the transactivation domain) were introduced into cultured acini with adenoviral vectors and utilized to evaluate the importance of c‐jun and AP‐1 signaling for growth. Both of these dominant negative constructs largely inhibited thymidine incorporation in cultured acinar cells, while a control virus expressing GFP had no effect. We conclude that cultured acinar cells can be used to model acinar cell growth that occurs during regeneration and the JNK cascade and c‐jun participate in stimulating this growth. This research is supported by NIH grant DK 59578 (J.A.W.).