Identification of hepatocyte growth factor activator (Hgfac) gene as a target of HNF1α in mouse β-cells

HNF1 alpha is a transcription factor that is expressed in pancreatic beta-cells and mutations of the HNF1 alpha gene cause a form of monogenic diabetes. To understand the role of HNF1 alpha in pancreatic beta-cells, we established the MIN6 beta-cell line that stably expressed HNF1 alpha-specific shRNA. Expression of the gene encoding hepatocyte growth factor (HGF) activator (Hgfac), a serine protease that efficiently activates HGF, was decreased in HNF1 alpha KD-MIN6 cells. Down-regulation of Hgfac expression was also found in the islets of HNF1 alpha (+/-) mice. Reporter gene analysis and the chromatin immunoprecipitation assay indicated that HNF1 alpha directly regulates the expression of Hgfac in beta-cells. It has been reported that HGF has an important influence on beta-cell mass and beta-cell function. Thus, HNE1 alpha might regulate beta-cell mass or function at least partly by modulating Hgfac expression. (C) 2012 Elsevier Inc. All rights reserved.