GATA-4 upregulates glucose-dependent insulinotropic polypeptide expression in cells of pancreatic and intestinal lineage
GATA-4 upregulates glucose-dependent insulinotropic polypeptide expression in cells of pancreatic and intestinal lineage
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DOI：
10.1016/j.mce.2008.01.024
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发表时间：
2008-06-11
影响因子：
4.1
通讯作者：
Wolfe, M. Michael
中科院分区：
文献类型：
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作者：
Jepeal, Lisa I.;Boylan, Michael O.;Wolfe, M. Michael
由于难以分离广泛分散的、产生 GIP 的肠内分泌 K 细胞，对葡萄糖依赖性促胰岛素多肽 (GIP) 表达的彻底检查受到阻碍。为了阐明 GIP 表达调节的分子机制，评估了 14 种肠道和胰腺细胞系是否适合检查 GIP 表达的研究。 STC-1 细胞和胰腺细胞系 PTC-3 均被发现表达 GIP mRNA 并分泌具有生物活性的 GIP。然而，PTC-3 细胞中 GIP mRNA 和生物活性肽的水平以及转染的 GIP 报告基因构建体的活性显着低于 STC-1 细胞。当分析 PTC-3 细胞中已知对 GIP 表达重要的转录因子时，检测到 PDX-1 和 ISL-1，但未检测到 GATA-4。小鼠十二指肠中 GIP-1 和 GATA-4 的双重染色证明了肠 K 细胞中 GATA-4 的表达。 PTC-3 细胞中 GATA-4 的外源表达导致 GIP 转录和分泌显着增加。最后，在 GTC-1 细胞（具有高内源性 GIP 表达的 STC-1 细胞亚群）中，通过 RNA 干扰抑制 GATA-4 导致 GIP 启动子活性显着减弱。我们的数据支持这样的假设：GATA-4 可能起到增强或增强 GIP 表达的作用，而不是充当 GIP 转录的启动子。 (c) 2008 Elsevier Ireland Ltd. 保留所有权利。
A thorough examination of glucose-dependent insulinotropic polypeptide (GIP) expression has been hampered by difficulty in isolating widely dispersed, GIP-producing enteroendocrine K-cells. To elucidate the molecular mechanisms governing the regulation of GIP expression, 14 intestinal and pancreatic cell lines were assessed for their suitability for studies examining GIP expression. Both STC-1 cells and the pancreatic cell line PTC-3 were found to express GIP mRNA and secrete biologically active GIP. However, levels of GIP mRNA and bioactive peptide and the activity of transfected GIP reporter constructs were significantly lower in PTC-3 than STC-1 cells. When PTC-3 cells were analyzed for transcription factors known to be important for GIP expression, PDX-1 and ISL-1, but not GATA-4, were detected. Double staining for GIP-I and GATA-4 in mouse duodenum demonstrated GATA-4 expression in intestinal K-cells. Exogenous expression of GATA-4 in PTC-3 cells led to marked increases in both GIP transcription and secretion. Lastly suppression of GATA-4 via RNA interference, in GTC-1 cells, a subpopulation of STC-1 cells with high endogenous GIP expression resulted in a marked an attenuation of GIP promoter activity. Our data support the hypothesis that GATA-4 may function to augment or enhance GIP expression rather than act as an initiator of GIP transcription. (c) 2008 Elsevier Ireland Ltd. All rights reserved.