Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Biochem Biophys Res Commun. 2012 Aug 31;425(3):619-24. doi: 10.1016/j.bbrc.2012.07.134. Epub 2012 Aug 1.
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.
HNF1α 是一种在胰腺 β 细胞中表达的转录因子，HNF1α 基因突变会导致一种单基因糖尿病。为了了解 HNF1α 在胰腺 β 细胞中的作用，我们建立了稳定表达 HNF1α 特异性 shRNA 的 MIN6 β 细胞系。编码肝细胞生长因子 (HGF) 激活剂 (Hgfac) 的基因表达在 HNF1α KD-MIN6 细胞中减少，Hgfac 是一种能有效激活 HGF 的丝氨酸蛋白酶。在 HNF1α (+/-) 小鼠的胰岛中也发现了 Hgfac 表达下调。报告基因分析和染色质免疫沉淀试验表明，HNF1α 可直接调节 β 细胞中 Hgfac 的表达。据报道，HGF 对 β 细胞质量和 β 细胞功能有重要影响。因此，HNF1α 可能至少部分通过调节 Hgfac 表达来调节 β 细胞质量或功能。
