title: Immunohistochemical study about the Flt-1/VEGFR1 expression in the gastrointestinal tract of mouse, rat, dog, swine and monkey.
abstract: Fms-like tyrosine kinase 1 (Flt-1) performs a subordinate effector role in mesenchymal angiogenesis and potentially serves an equally important functional role as a self-contained receptor in epithelial cells. In both endothelial cells and epithelial cells, Flt-1/vascular endothelial growth factor receptor 1 (VEGFR1) downstream signalling is involved in regulating cellular processes such as cytoskeletal changes and cellular survival protection. Cellular renewal of the gastrointestinal mucosa is based on these processes and might involve Flt-1/VEGFR1 pathway activities; the molecular mechanisms regulating these cellular dynamics remain unclear. This study was performed to investigate the presence and distribution of Flt-1/VEGFR1 in epithelial cells of the gastrointestinal tract by immunohistochemistry (IHC). Gastrointestinal tissues were taken from eight anatomical sites from mouse, rat, dog, swine and monkey. Present results revealed a cytosolic Flt-1/VEGFR1 staining pattern in mucosal epithelial cells for all investigated species. Non-epithelial structures also displayed a distinct Flt-1/VEGFR1 positivity and included vascular smooth muscle walls, enteric smooth muscle layers, the enteric nervous system and capillary endothelial cells. Diverse intensities of the Flt-1/VEGFR1 binding reaction within each species were observed in the intestinal mucosa with a strong immunoreaction in enterocytes and with a low protein expression in the ileum in most species. Crypt cells in the large intestine were mostly negative for Flt-1/VEGFR1. A peculiar and mainly intranuclear antibody binding reaction was found in Brunner's gland epithelial cells of mouse and rat whereas Brunner's glands of dog, swine and monkey remained completely negative. These results indicate a potential involvement of Flt-1/VEGFR1 in normal restitution of gastrointestinal structures in the species studied. Additionally, intranuclear Flt-1/VEGFR1 antibody binding in Brunner's glands of rodents may suggest a nuclear translocation of the transmembrane VEGFR1 which has not previously been described.
authors.affiliation: Department of Pathology, Novartis Pharma AG, MUT-2881.4.07, 4002 Basle, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Hagedorn
authors.forename: P-G
authors.initials: PG
authors.lastname: Germann
authors.forename: U
authors.initials: U
authors.lastname: Junker-Walker
authors.forename: A
authors.initials: A
authors.lastname: Tomovic
authors.forename: W
authors.initials: W
authors.lastname: Seewald
authors.forename: A
authors.initials: A
authors.lastname: Polkinghorne
authors.forename: A
authors.initials: A
authors.lastname: Pospischil
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D041981:Gastrointestinal Tract / Q000737:chemistry* / Q000166:cytology; D000882:Haplorhini; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D051381:Rats; D013045:Species Specificity; D013552:Swine; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis*
chemical_list: D040281:Vascular Endothelial Growth Factor Receptor-1