PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells.
PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells.
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PDX-1 诱导肠上皮样 IEC-6 分化为胰岛素产生细胞。
DOI：
10.2337/diabetes.51.8.2505
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发表时间：
2002
期刊：
影响因子：
7.7
通讯作者：
M. Hori
中科院分区：
文献类型：
--
作者：
Shigeru Yoshida;Y. Kajimoto;T. Yasuda;H. Watada;Y. Fujitani;H. Kosaka;T. Gotow;T. Miyatsuka;Y. Umayahara;Y. Yamasaki;M. Hori
含有转录因子PDX-1的同源结构域可以在一些非β细胞中诱导β细胞特异性基因表达，因此可能对未来的糖尿病基因/细胞治疗有用。转录因子介导的β细胞样分化诱导的潜在靶器官或组织是肠上皮细胞。就基因递送的可及性以及与胰腺原基发育背景的相似性而言，它们比其他组织和器官具有一定的优点。在这项研究中，我们使用了肠上皮衍生的细胞系，IEC-6细胞，并研究了PDX-1在这些细胞中表达的可能影响。通过PDX-1基因的外源性表达，IEC-6细胞开始表达多种β细胞特异性基因，如胰淀素、葡萄糖激酶和Nkx6.1，这些基因在原始IEC-6细胞中没有发现。胰岛素基因的表达，这是失踪最初甚至在PDX-1转染的IEC-6细胞，成为检测时，细胞移植到大鼠的肾包膜下。当PDX-1（+）IEC-6细胞保持在体外时，用β细胞素处理也可以赋予它们胰岛素基因表达。虽然胰岛素分泌颗粒变得可见的电子显微镜，他们分泌的葡萄糖浓度无关。在PDX-1（-）IEC-6细胞中未观察到胰岛素基因表达的体内或体外诱导。因此，我们目前的观察结果证明了肠上皮细胞作为糖尿病基因/细胞治疗工具的效力，并为PDX-1在驱动非β细胞中的β细胞样分化中的效力提供了进一步的支持。
A homeodomain containing transcription factor PDX-1 can induce beta-cell-specific gene expressions in some non-beta-cells and may therefore be useful for future diabetes gene/cell therapy. Among the potential target organs or tissues for transcription factor-mediated induction of beta-cell-like differentiation are the intestinal epithelial cells. They have certain merits over other tissues and organs in terms of accessibility for gene delivery and of similarity in developmental background to the pancreatic primordium. In this study, we used an intestinal epithelium-derived cell line, IEC-6 cells, and investigated the possible effects of PDX-1 expression in those cells. By exogenous expression of the PDX-1 gene, IEC-6 cells started expressing multiple beta-cell-specific genes such as amylin, glucokinase, and Nkx6.1, which were not found in the original IEC-6 cells. Insulin gene expression, which was missing initially even in the PDX-1-transfected IEC-6 cells, became detectable when the cells were transplanted under the renal capsule of a rat. When the PDX-1(+) IEC-6 cells were kept in vitro, treatment with betacellulin could also confer insulin gene expression to them. Although insulin secretory granules became visible by electron microscopy, they were secreted regardless of glucose concentration. The in vivo or in vitro inductions of the insulin gene expression were not observed in the PDX-1(-) IEC-6 cells. Thus, our present observations demonstrate the potency of intestinal epithelial cells as a tool for diabetes gene/cell therapy and provide further support for the potency of PDX-1 in driving beta-cell-like differentiation in non-beta-cells.
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DOI：
10.1073/pnas.94.8.3560
发表时间：
1997-04-15
影响因子：
11.1
作者：
Mutoh, H;Fung, BP;Leiter, AB
通讯作者：
Leiter, AB
DOI：
10.1152/ajpgi.1999.277.5.g1027
发表时间：
1999-11-01
影响因子：
4.5
作者：
Quaroni, A;Tian, JQ;Podolsky, DK
通讯作者：
Podolsky, DK
小鼠胚胎卵黄囊细胞促进骨髓高增殖潜能集落形成细胞的体外增殖。
影响因子：
20.3
作者：
Yoder,MC;King,B;Hiatt,K;Williams,DA
通讯作者：
Williams,DA
影响因子：
4.8
作者：
Gerrish, K;Grannon, M;Stein, R
通讯作者：
Stein, R