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

Didier Sanchez, Cathy M. Mueller, Michael E. Zenilman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)572-577
Number of pages6
JournalPancreas
Volume38
Issue number5
DOIs
StatePublished - Jul 1 2009

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Keywords

  • AR42J
  • Acinar cells
  • Antisense inhibition
  • Pancreatic reg I
  • Sense overexpression

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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