Expression and modulation of p42/p44 MAPKs and cell cycle regulatory proteins in rat pancreas regeneration

Pancreatic growth occurs after CCK, CCK-induced pancreatitis, and pancreate ctomy; the mechanisms involved remain unknown. This study evaluates mitogen -activated protein kinase (MAPK) activation and expression of cell cycle re gulatory proteins after pancreatectomy to understand the cellular and molec ular mechanisms involved in pancreas regeneration. Rats were killed 1-12 da ys after pancreatectomy, and p42/p44 MAPK activation, expression of the cyc lins D and E, cyclin-dependent kinase (Cdk)-2 activity, retinoblastoma prot ein (pRb) hyperphosphorylation, and expression of the cyclin kinase inhibit ors p15, p21, and p27 were examined. Pancreatic remnants exhibited sustaine d p42/p44 MAPK activation within 8 h. Cyclins D1 and E showed maximal expre ssion after 2 and 6 days, coinciding with maximal hyperphosphorylation of p Rb and Cdk2 activity. The expression of p15 vanished after 12 h, p27 disapp eared gradually, and p21 increased early. The p27 complexed with Cdk2 disso ciated after 2 days, whereas p21 associated in a reverse fashion. In conclu sion, sustained activation of p42/p44 MAPKs and Cdk2 along with overexpress ion of cyclins DI and E and reduction of p15 and p27 cyclin inhibitors occu rred early after pancreatectomy and are active factors involved in signalin g that leads to pancreas regeneration.