Sharma A, Zangen D H, Reitz P, Taneja M, Lissauer M E, Miller C P, Weir G C, Habener J F, Bonner-Weir S
E.P. Joslin Research Laboratories, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Diabetes. 1999 Mar;48(3):507-13. doi: 10.2337/diabetes.48.3.507.
Islet duodenal homeobox 1 (IDX-1/PF-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 Px, sham Px, 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 Px or sham Px but was easily detected at 2 and 3 days after Px. Similarly, IDX-1 immunostaining was barely detectable in sham or unoperated ducts but was strong in ducts at 2-3 days after Px. 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 d after Px 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.
胰岛十二指肠同源盒蛋白1（IDX-1/PF-1/STF-1/PDX-1）是一种能反式激活胰岛素启动子的同源结构域蛋白，靶向基因敲除实验表明它是胰腺发育所必需的。90%胰腺切除术后，成年胰腺会经历一个重现胚胎发育过程的再生过程，首先是胰管上皮细胞的增殖爆发。在这个模型中，通过半定量逆转录-聚合酶链反应在分离的胰管总RNA中检测到IDX-1 mRNA，其水平仅为分离胰岛的10%。胰腺切除、假手术和未手术大鼠的胰管中IDX-1 mRNA水平无显著差异，且术后也不随时间变化。通过免疫印迹分析，在胰腺切除或假手术后1天和7天，这些胰管中仅能微弱检测到IDX-1蛋白，但在胰腺切除后2天和3天则很容易检测到。同样地，在假手术或未手术的胰管中几乎检测不到IDX-1免疫染色，但在胰腺切除后2 - 3天的胰管中染色很强。IDX-1免疫染色的增加与BrdU掺入（增殖）的增加一致。这些结果表明胰管中IDX-1表达存在转录后调控。此外，胰腺切除后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，在胰腺再生过程中，IDX-1在新分裂的导管细胞以及胰岛中均上调。IDX-1表达增强的时间表明，IDX-1在再生起始阶段并不重要，但可能参与导管细胞向β细胞的分化。
