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| The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration |
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| Author(s): Sharma A, Zangen DH, Reitz P, Taneja M, Lissauer ME, Miller CP, Weir GC, Habener JF, Bonner-Weir S |
| Source: DIABETES Volume: 48 Issue: 3 Pages: 507-513 Published: MAR 1999 |
| Times Cited: 201 References: 54 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Bonner-Weir, S (reprint author), Joslin Diabet Ctr, EP Joslin Res Labs, 1 Joslin Pl, Boston, MA 02215 USA |
Addresses:
1. Joslin Diabet Ctr, EP Joslin Res Labs, Boston, MA 02215 USA
2. Harvard Univ, Sch Med, Dept Med, Boston, MA USA
3. Massachusetts Gen Hosp, Dept Pediat Endocrinol, Boston, MA 02114 USA
4. Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA
5. Inst Genet, EGRP Grp, Cambridge, MA USA |
| Publisher: AMER DIABETES ASSOC, 1660 DUKE ST, ALEXANDRIA, VA 22314 USA |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: 170VE |
| ISSN: 0012-1797 |
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