title: Identification of hepatocyte growth factor activator (Hgfac) gene as a target of HNF1α in mouse β-cells.
abstract: HNF1α is a transcription factor that is expressed in pancreatic β-cells and mutations of the HNF1α gene cause a form of monogenic diabetes. To understand the role of HNF1α in pancreatic β-cells, we established the MIN6 β-cell line that stably expressed HNF1α-specific shRNA. Expression of the gene encoding hepatocyte growth factor (HGF) activator (Hgfac), a serine protease that efficiently activates HGF, was decreased in HNF1α KD-MIN6 cells. Down-regulation of Hgfac expression was also found in the islets of HNF1α (+/-) mice. Reporter gene analysis and the chromatin immunoprecipitation assay indicated that HNF1α directly regulates the expression of Hgfac in β-cells. It has been reported that HGF has an important influence on β-cell mass and β-cell function. Thus, HNF1α might regulate β-cell mass or function at least partly by modulating Hgfac expression.
authors.affiliation: Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ohki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshizawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamamura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D034741:RNA, Small Interfering; C081092:HGF activator; D012697:Serine Endopeptidases