The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration

Arun Sharma, David H. Zangen, Petra Reitz, Monica Taneja, Matthew E. Lissauer, Christopher P. Miller, Gordon C. Weir, Joel F. Habener, Susan Bonner-Weir*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

303 Scopus citations

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 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 β-cells.

Original languageAmerican English
Pages (from-to)507-513
Number of pages7
JournalDiabetes
Volume48
Issue number3
DOIs
StatePublished - 1999
Externally publishedYes

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