PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells
PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells
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DOI：
10.2337/diabetes.52.7.1732
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发表时间：
2003-07-01
期刊：
影响因子：
7.7
通讯作者：
Bonner-Weir, S
中科院分区：
文献类型：
--
作者：
Noguchi, H;Kaneto, H;Bonner-Weir, S
胰腺和十二指肠同源框因子-1（PDX-1），也称为IDX-1/STF-1/IPF 1，是一种含有同源结构域的转录因子，在调节胰腺发育和胰岛素基因转录中起核心作用。此外，即使在成人中，PDX-1也与胰岛新生和胰岛素产生细胞从祖细胞的分化有关。在这里，我们首次报告，PDX-1蛋白可以渗透细胞，由于其结构中的一个类似于拟南芥的蛋白转导结构域序列，并且转导的PDX-1功能与内源性PDX-1相似;它结合到胰岛素启动子并激活其表达。PDX-1蛋白还可以渗透到分离的胰岛中，这导致胰岛素基因表达的刺激。此外，PDX-1蛋白转导到被认为是胰岛祖细胞的胰管培养物中，诱导胰岛素基因表达。这些数据表明，PDX-1蛋白转导可能是一种安全和有价值的策略，用于增强胰岛素基因转录和促进导管祖细胞分化为胰岛素产生细胞，而不需要基因转移技术。
The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology.