Division of Gastroenterology and Nutrition, Department of Medicine, Children's Hospital Boston, Boston, Massachusetts, USA.
Gastroenterology. 2011 Apr;140(4):1219-1229.e1-2. doi: 10.1053/j.gastro.2011.01.033. Epub 2011 Jan 21.
BACKGROUND & AIMS: GATA transcription factors regulate proliferation, differentiation, and gene expression in multiple organs. GATA4 is expressed in the proximal 85% of the small intestine and regulates the jejunal-ileal gradient in absorptive enterocyte gene expression. GATA6 is co-expressed with GATA4 but also is expressed in the ileum; its function in the mature small intestine is unknown.
We investigated the function of GATA6 in small intestine using adult mice with conditional, inducible deletion of Gata6, or Gata6 and Gata4, specifically in the intestine.
In ileum, deletion of Gata6 caused a decrease in crypt cell proliferation and numbers of enteroendocrine and Paneth cells, an increase in numbers of goblet-like cells in crypts, and altered expression of genes specific to absorptive enterocytes. In contrast to ileum, deletion of Gata6 caused an increase in numbers of Paneth cells in jejunum and ileum. Deletion of Gata6 and Gata4 resulted in a jejunal and duodenal phenotype that was nearly identical to that in the ileum after deletion of Gata6 alone, revealing common functions for GATA6 and GATA4.
GATA transcription factors are required for crypt cell proliferation, secretory cell differentiation, and absorptive enterocyte gene expression in the small intestinal epithelium.
GATA 转录因子调节多个器官的增殖、分化和基因表达。GATA4 在小肠近端的 85%表达，并调节吸收性肠细胞基因表达的空肠-回肠梯度。GATA6 与 GATA4 共同表达，但也在回肠中表达；其在成熟小肠中的功能尚不清楚。
我们使用成年小鼠中条件性、诱导性缺失 Gata6 或 Gata6 和 Gata4，特别是在肠道中，研究了 GATA6 在小肠中的功能。
在回肠中，Gata6 的缺失导致隐窝细胞增殖和肠内分泌细胞和 Paneth 细胞数量减少，隐窝中杯状细胞数量增加，以及吸收性肠细胞特异性基因表达改变。与回肠相反，Gata6 的缺失导致空肠和回肠中 Paneth 细胞数量增加。Gata6 和 Gata4 的缺失导致空肠和十二指肠表型与 Gata6 缺失后回肠的表型几乎相同，表明 GATA6 和 Gata4 具有共同的功能。
GATA 转录因子是小肠上皮隐窝细胞增殖、分泌细胞分化和吸收性肠细胞基因表达所必需的。
