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-gamma transgenic model for regeneration within the pancreas lead us to propose that these factors are important during pancreatic regeneration. In this study, we have assessed the influence of two growth factors within the pancreas, epidermal growth factor (EGF) and keratinocyte growth factor (KGF), by ectopically expressing these proteins under the control of the human insulin promoter in transgenic mice. This beta-cell-targeted expression of either EGF or KGF resulted in significant morphological changes, including cellular proliferation and disorganized islet growth. Intercrossing the individual Ins-EGF and Ins-KGF transgenic mice resulted in more profound changes in pancreatic morphology including proliferation of pancreatic cells and extensive intra-islet fibrosis. Insulin-producing beta-cells were found in some of the ducts of older Ins-EGF and Ins-EGFxKGF transgenic mice, and amylase-producing cells were observed within the islet structures of the double transgenic mice. These data suggest that both EGF and KGF are capable of affecting pancreatic differentiation and growth, and that co-expression of these molecules in islets has a more substantial impact on the pancreas than does expression of either growth factor alone.
Krakowski
M L
ML
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Kritzik
M R
MR
Jones
E M
EM
Krahl
T
T
Lee
J
J
Arnush
M
M
Gu
D
D
Mroczkowski
B
B
Sarvetnick
N
N
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000033:anatomy & histology / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D001786:Blood Glucose; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor