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

Abstract

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.