Shiimura Yuki, Ohgusu Hideko, Sato Takahiro, Kojima Masayasu
Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Fukuoka 839-0864, Japan.
Int J Endocrinol. 2015;2015:580908. doi: 10.1155/2015/580908. Epub 2015 Jan 28.
To examine the gene expression of ghrelin, a growth hormone releasing and appetite stimulating hormone from stomach, we constructed human ghrelin promoter-reporter vectors and analyzed the promoter activity. The ghrelin promoter activity was high when cultured cells that express ghrelin mRNA endogenously like TT or ECC10 cells were used, indicating that these cells contain factors necessary for full expression of the human ghrelin gene. The human ghrelin promoter contains both positive and negative regulatory regions. A transient decrease of the promoter activity was found when the reporter vector with the -1600 fragment of the human ghrelin promoter was transfected into cultured cells. We then examined the effect of several transcription factors on the ghrelin promoter activity and found that NF-κB suppressed and that Nkx2.2, a homeodomain-containing transcription factor that is important for ghrelin cell development in pancreas, activates the promoter activity. These transcription factors may be possible targets for the control of ghrelin gene expression.
为了检测胃中一种释放生长激素并刺激食欲的激素——胃饥饿素的基因表达，我们构建了人胃饥饿素启动子-报告载体并分析了启动子活性。当使用像TT或ECC10细胞这样内源性表达胃饥饿素mRNA的培养细胞时，胃饥饿素启动子活性很高，这表明这些细胞含有充分表达人胃饥饿素基因所需的因子。人胃饥饿素启动子包含正调控区和负调控区。当将携带人胃饥饿素启动子-1600片段的报告载体转染到培养细胞中时，发现启动子活性短暂下降。然后我们检测了几种转录因子对胃饥饿素启动子活性的影响，发现核因子κB起抑制作用，而Nkx2.2（一种对胰腺中胃饥饿素细胞发育很重要的含同源异型域的转录因子）激活启动子活性。这些转录因子可能是控制胃饥饿素基因表达的潜在靶点。
