The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration
The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration
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DOI：
10.2337/diabetes.48.3.507
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发表时间：
1999-03-01
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：
Sharma, A;Zangen, DH;Bonner-Weir, S
胰岛十二指肠同源框1（IDX-1/IPF-1/STF-1/PDX-1），一种反式激活胰岛素启动子的同源域蛋白，已通过靶向基因切除显示为胰腺发育所需。90%胰腺切除术（Px）后，成人胰腺再生的过程重演胚胎发育，开始在总胰管上皮细胞的增殖爆发。在这个模型中，IDX-1 mRNA的检测通过半定量逆转录-聚合酶链反应在总RNA中从分离的共同胰腺导管的水平10%的那些分离的胰岛。IDX-1的mRNA水平没有显着差异的Pr，假Pr，和未手术的大鼠，并没有随着手术后的时间而变化。通过免疫印迹分析，Pr或假Pr后1天和7天，在这些导管中仅微弱地检测到IDX-1蛋白，但在Pr后2天和3天很容易检测到。同样，IDX-1免疫染色在假手术或未手术的导管中几乎检测不到，但在Pr后2-3天，导管中的IDX-1免疫染色较强。IDX-1免疫染色的增加紧随BrdU掺入（增殖）的增加。这些结果表明IDX-1在导管中表达的转录后调节。此外，Pr后3-7天分离的胰岛显示出比对照胰岛更高的IDX-1蛋白表达。因此，在胰腺再生中，IDX-1在新分裂的导管细胞以及胰岛中上调。IDX-1表达增强的时机意味着IDX-1在再生的起始中不重要，但可能参与导管细胞向β细胞的分化。
Islet duodenal homeobox 1 (IDX-1/IPF-1/STF-1/PDX-1), a homeodomain protein that transactivates the insulin promoter, has been shown by targeted gene ablation to be required for pancreatic development. After 90% pancreatectomy (Px), the adult pancreas regenerates in a process recapitulating embryonic development, starting with a burst of proliferation in the epithelium of the common pancreatic duct. In this model, IDX-1 mRNA was detected by semiquantitative reverse transcription-polymerase chain reaction in total RNA from isolated common pancreatic ducts at levels 10% of those of isolated islets. The IDX-1 mRNA levels were not significantly different for common pancreatic ducts of Pr, sham Pr, and unoperated rats and did not change with time after surgery. By immunoblot analysis, IDX-1 protein was only faintly detected in these ducts 1 and 7 days after Pr or sham Pr but was easily detected at 2 and 3 days after Pr. Similarly, IDX-1 immunostaining was barely detectable in sham or unoperated ducts but was strong in ducts at 2-3 days after Pr. The increase of IDX-1 immunostaining followed that of BrdU incorporation (proliferation). These results indicate a posttranscriptional regulation of the IDX-1 expression in ducts. In addition, islets isolated 3-7 days after Pr showed higher IDX-1 protein expression than control islets. Thus, in pancreatic regeneration IDX-1 is upregulated in newly divided ductal cells as well as in islets. The timing of enhanced expression of IDX-1 implies that IDX-1 is not important in the initiation of regeneration but may be involved in the differentiation of ductal cells to beta-cells.