Pancreatic Regenerating Gene I and Acinar Cell Differentiation

Abstract

Objectives Pancreatic 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 cDNA in sense (SS) or antisense (AS) orientation. Levels of mRNA and protein expression were examined by Western blotting and Real Time-PCR. Results Expression of reg I was confirmed in sense or antisense clones. AR42J transfected with SS demonstrated more acinar-like phenotype while those transfected with AS showed a less differentiated state. Specifically, amylase mRNA and protein levels increased in SS cells while AS cells showed increased PDX-1 and insulin mRNAs and cytokeratin protein. Conversely, cytokeratin and PDX-1 were depressed in SS cells. Conclusions These data demonstrate that in acinar cells, reg I over-expression is linked to acinar cell differentiation, while 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 de-differentiate and move towards becoming other pancreatic cells.

Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma

“…The REG1A gene product belongs to a family of REG (regenerating) glycoproteins, which are expressed in pancreatic acinar cells and acts as both autocrine and paracrine growth factor (22), (23). The REG protein(s) are expressed during islet cell regeneration (24), (25), but are also potentially associated with differentiation and maintenance of an exocrine phenotype (26), (27). REG1 (non-specified) expression has been reported previously in about 25% of PDACs (n=20) (28), while we observed strong expression of REG1A in 73% of the cases examined here.…”

Regenerating Islet-derived 1α (Reg-1α) Protein Is New Neuronal Secreted Factor That Stimulates Neurite Outgrowth via Exostosin Tumor-like 3 (EXTL3) Receptor

“…Reg-1␣ is involved in proliferation and differentiation of liver, pancreatic, gastric, and intestinal cells (6,22) and has been associated with differentiation/dedifferentiation of pancreatic acinar cells without any effect on cell proliferation (23,24). Here, we used primary embryonic hippocampal neurons (E17.5; 2 days in vitro) and two cell lines (PC12 cells, which are derived from a rat pheochromocytoma and reversibly respond to NGF by induction of the neuronal phenotype, and N2a, which are derived from a neuroblastoma and belong to a neural lineage) to investigate the expression, localization, and functions of Reg-1␣ in nerve cells.…”

Proteomic analysis of pancreatic juice for the identification of biomarkers of pancreatic cancer

“…The reg gene family is a multigene family grouped into four subclasses, types I, II, III, and IV (Legoffic et al 2009;Okamoto 1999). Among them, REG1a plays a role in cellular differentiation of the pancreas and is mitogenic to ductal and beta cells (Sanchez et al 2009). It also has been detected in cholangiocarcinoma, gastric cancer, and pancreatic cancers (Harada et al 2001;Zhou et al 2010;Sekikawa et al 2005).…”