Transgenic expression of epidermal growth factor and keratinocyte growth factor in beta-cells results in substantial morphological changes

The upregulation of a limited number of growth factors in our interferon-ga mma transgenic model for regeneration within the pancreas lead us to propos e that these factors are important during pancreatic regeneration. In this study, we have assessed the influence of two growth factors within the panc reas, epidermal growth factor (EGF) and keratinocyte growth factor (KGF), b y ectopically expressing these proteins under the control of the human insu lin promoter in transgenic mice. This beta-cell-targeted expression of eith er EGF or KGF resulted in significant morphological changes, including cell ular proliferation and disorganized islet growth. Intercrossing the individ ual Ins-EGF and Ins-KGF transgenic mice resulted in more profound changes i n pancreatic morphology including proliferation of pancreatic cells and ext ensive intra-islet fibrosis. Insulin-producing beta-cells were found in som e of the ducts of older Ins-EGF and Ins-EGF x KGF transgenic mice, and amyl ase-producing cells were observed within the islet structures of the double transgenic mice. These data suggest that both EGF and KGF are capable of a ffecting pancreatic differentiation and growth, and that co-expression of t hese molecules in islets has a more substantial impact on the pancreas than does expression of either growth factor alone.