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

Pancreas. 2009 Jul;38(5):572-7. doi: 10.1097/mpa.0b013e3181a1d9f9.

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 beta 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amylases / genetics
  • Amylases / metabolism
  • Animals
  • Blotting, Western
  • Carcinoma, Acinar Cell / genetics
  • Carcinoma, Acinar Cell / metabolism
  • Carcinoma, Acinar Cell / pathology
  • Cell Differentiation*
  • Cell Line, Tumor
  • Cell Lineage*
  • Cell Proliferation
  • DNA, Complementary / genetics
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Insulin / genetics
  • Insulin / metabolism
  • Lithostathine / genetics
  • Lithostathine / metabolism*
  • Microscopy, Phase-Contrast
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transfection

Substances

  • DNA, Complementary
  • Homeodomain Proteins
  • Insulin
  • Lithostathine
  • RNA, Messenger
  • Reg1a protein, rat
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Amylases