Sanchez Didier, Mueller Cathy M, Zenilman Michael E
Department of Surgery, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
Pancreas. 2009 Jul;38(5):572-7. doi: 10.1097/mpa.0b013e3181a1d9f9.
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.
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.
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.
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.
胰腺再生基因I（reg I）与细胞分化有关。腺泡细胞可转分化为其他胰腺来源的细胞，我们推测reg I细胞内水平的变化会影响分化状态。
我们用含有reg I完整编码序列的质粒转染AR42J细胞，并分离出具有正义（SS）或反义（AS）方向互补DNA的克隆。通过蛋白质免疫印迹法和实时聚合酶链反应检测信使核糖核酸（mRNA）水平和蛋白质表达。
在SS或AS克隆中证实了reg I的表达。用SS转染的AR42J表现出更多腺泡样表型，而用AS转染的细胞表现出分化程度较低的状态。具体而言，SS细胞中淀粉酶mRNA和蛋白质水平升高，而AS细胞中胰腺和十二指肠同源盒1（Pdx1）、胰岛素mRNA以及细胞角蛋白蛋白质水平升高。相反，SS细胞中的细胞角蛋白和Pdx1水平降低。
这些数据表明，在腺泡细胞中，reg I过表达与腺泡细胞分化有关，而reg I的抑制则导致β细胞以及可能的导管表型。腺泡细胞中reg I的表达对于维持胰腺细胞谱系很重要，当其降低时，细胞可去分化并向成为其他胰腺细胞的方向发展。
