Gastrin stimulates expression of plasminogen activator inhibitor-1 in gastric epithelial cells

• DOI: 10.1152/ajpgi.00527.2010
• Publication Date: 2010-12-30T21:00:00Z
• Authors: Kristin G. Nørsett; Islay Steele; Cedric Duval; Stephen J. Sammut; Senthil V. M. Mur...; Susan Kenny; Lucille Rainbow; Rod Dimaline; Graham J. Dockray; D. Mark Pritchard; Andrea Varro
• Keywords: Plasminogen activator inhibitor-1

Plasminogen activator inhibitor (PAI)-1 is associated with cancer progression, fibrosis and thrombosis. It expressed in the stomach but mechanisms controlling its expression there, biological role, are uncertain. We sought to define role of gastrin regulating PAI-1 determine relevance for gastrin-stimulated cell migration invasion. In gastric biopsies from subjects elevated plasma gastrin, abundances PAI-1, urokinase plasminogen (uPA), uPA receptor (uPAR) mRNAs measured by quantitative PCR were increased compared concentrations reference range. patients hypergastrinemia due autoimmune chronic atrophic gastritis, there was abundance uPA, uPAR that reduced octreotide or antrectomy. Immunohistochemistry revealed localization parietal cells enterochromaffin-like micronodular neuroendocrine tumors hypergastrinemic subjects. Transcriptional studied using a PAI-1-luciferase promoter-reporter construct transfected into AGS-G(R) cells. There time- concentration-dependent increase response reversed inhibitors PKC MAPK pathways. Boyden chamber assays, recombinant inhibited invasion, small interfering RNA treatment responses gastrin. conclude which may act restrain