Pancreatic regenerating gene I and acinar cell differentiation: Influence on cellular lineage

OBJECTIVES: Pancreatic regenerating gene I (reg I) has been implicated in cellular differentiation. Acinar cells can transdifferentiate into other pancreatic-derived cells, and we postulated that changes in intracellular levels of reg I would affect the state of differentiation. METHODS: We transfected AR42J cells with a plasmid containing the entire coding sequence of reg I and isolated clones with complementary DNA in sense (SS) or antisense (AS) orientation. Levels of messenger RNA (mRNA) and protein expression were examined by Western blotting and real-time polymerase chain reaction. RESULTS: Expression of reg I was confirmed in SS or AS clones. AR42J transfected with SS demonstrated more acinarlike phenotype, whereas those transfected with AS showed a less differentiated state. Specifically, amylase mRNA and protein levels increased in SS cells, whereas AS cells showed increased pancreatic and duodenal homeobox 1 (Pdx1) and insulin mRNAs and cytokeratin protein. Conversely, cytokeratin and Pdx1 were depressed in SS cells. CONCLUSIONS: These data demonstrate that in acinar cells, reg I overexpression is linked to acinar cell differentiation, whereas inhibition of reg I leads to β cell and possibly ductal phenotype. Reg I expression in acinar cells is important in maintaining pancreatic cell lineage, and when decreased, cells can dedifferentiate and move toward becoming other pancreatic cells.