Canadian Institutes of Health Research Team on Digestive Epithelium, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke J1H 5N4, QC, Canada.
World J Gastroenterol. 2012 Apr 14;18(14):1579-89. doi: 10.3748/wjg.v18.i14.1579.
To investigate the impact of phosphatase and tensin homolog (Pten) in the specification of intestinal enteroendocrine subpopulations.
Using the Cre/loxP system, a mouse with conditional intestinal epithelial Pten deficiency was generated. Pten mutant mice and controls were sacrificed and small intestines collected for immunofluorescence and quantitative real-time polymerase chain reaction. Blood was collected on 16 h fasted mice by cardiac puncture. Enzyme-linked immunosorbent assay was used to measure blood circulating ghrelin, somatostatin (SST) and glucose-dependent insulinotropic peptide (GIP) levels.
Results show an unexpected dual regulatory role for epithelial Pten signalling in the specification/differentiation of enteroendocrine cell subpopulations in the small intestine. Our data indicate that Pten positively regulates chromogranin A (CgA) expressing subpopulations, including cells expressing secretin, ghrelin, gastrin and cholecystokinin (CCK). In contrast, Pten negatively regulates the enteroendocrine subtype specification of non-expressing CgA cells such as GIP and SST expressing cells.
The present results demonstrate that Pten signalling favours the enteroendocrine progenitor to specify into cells expressing CgA including those producing CCK, gastrin and ghrelin.
研究磷酸酶和张力蛋白同系物（Pten）在肠道内分泌细胞亚群特化中的作用。
利用 Cre/loxP 系统，构建了条件性肠道上皮细胞 Pten 缺失的小鼠模型。处死 Pten 突变小鼠和对照组小鼠，收集小肠用于免疫荧光和实时定量聚合酶链反应。对禁食 16 小时的小鼠进行心脏穿刺采血，采用酶联免疫吸附试验测定血液中环肠肽（ghrelin）、生长抑素（SST）和葡萄糖依赖性胰岛素释放肽（GIP）水平。
结果表明上皮细胞 Pten 信号在小肠内分泌细胞亚群的特化/分化中具有出人意料的双重调节作用。我们的数据表明，Pten 正向调节嗜铬粒蛋白 A（CgA）表达亚群，包括分泌素、ghrelin、胃泌素和胆囊收缩素（CCK）表达细胞。相比之下，Pten 负向调节不表达 CgA 的内分泌细胞亚群的特化，如表达 GIP 和 SST 的细胞。
本研究结果表明，Pten 信号有利于内分泌前体细胞特化成为表达 CgA 的细胞，包括产生 CCK、胃泌素和 ghrelin 的细胞。
