Pancreatic expression of keratinocyte growth factor leads to differentiation of islet hepatocytes and proliferation of duct cells

Keratinocyte growth factor, (KGF), a member of the fibroblast growth factor (FGF) family, is involved In wound healing. It also promotes the different iation of many epithelial tissues and proliferation of epithelial cells as well as pancreatic duct cells. Additionally, many members of the highly hom ologous FGF family (including KGF), influence both growth and cellular morp hology In the developing embryo. We have previously observed elevated level s of KGF in our interferon-gamma transgenic mouse model of pancreatic regen eration. To understand the role of KGF in pancreatic differentiation, we ge nerated insulin promoter-regulated KGF transgenic mice. Remarkably, we have found that ectopic KGF expression resulted In the emergence of hepatocytes within the islets of Langerhans in the pancreas. Additionally, significant intraislet duct cell proliferation in the pancreata of transgenic KGF mice was observed. The unexpected appearance of hepatocytes and proliferation o f intraislet duct cells in the pancreata of these mice evidently stemmed di rectly from local exposure to KGF.