Zhan Xiao-Rong, Li Xin-Yu, Liu Xiao-Min, Zhou Jian-Hua, Yang Yu-Ling, Yi Ran, Zhang Jing, Yang Bao-Feng
Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province, PR China.
Biochem Biophys Res Commun. 2009 May 1;382(2):375-80. doi: 10.1016/j.bbrc.2009.03.029. Epub 2009 Mar 11.
The present study was conducted to identify effective factors that could induce differentiation of pancreatic ductal epithelial cells (PDECs) into insulin-producing cells. We examined the effect of hepatocyte growth factor (HGF) and betacellulin-delta4 (BTC-delta4) on PDECs. We isolated PDECs from adult rats and stimulated them with HGF and BTC-delta4 for 28days. We observed several characteristics of PDECs after induction, including functional changes in PDECs, differentiation rate, and expression levels of critical transcription factors. We observed that insulin content and glucose-induced insulin secretion were significantly higher in induced PDECs compared to control PDECs. The expression of markers specific to mature beta-cells, i.e., insulin and glucose transporter-2 (GLUT2) was also observed. An analysis of the expression of different transcription factors (PDX-1, Ngn3, NeuroD, and Pax4) revealed that cell-specific gene expression patterns varied from 7 to 28days after treatment. Hence, we conclude that treatment with a combination of HGF and BTC-delta4 is effective in inducing the differentiation of PDECs into insulin-secreting cells.
本研究旨在确定可诱导胰腺导管上皮细胞（PDEC）分化为胰岛素分泌细胞的有效因素。我们检测了肝细胞生长因子（HGF）和β细胞ulin-δ4（BTC-δ4）对PDEC的作用。我们从成年大鼠中分离出PDEC，并用HGF和BTC-δ4刺激它们28天。我们观察了诱导后PDEC的几个特征，包括PDEC的功能变化、分化率以及关键转录因子的表达水平。我们观察到，与对照PDEC相比，诱导后的PDEC中胰岛素含量和葡萄糖诱导的胰岛素分泌显著更高。还观察到了成熟β细胞特异性标志物即胰岛素和葡萄糖转运蛋白2（GLUT2）的表达。对不同转录因子（PDX-1、Ngn3、NeuroD和Pax4）表达的分析表明，治疗后7至28天细胞特异性基因表达模式有所不同。因此，我们得出结论，联合使用HGF和BTC-δ4治疗可有效诱导PDEC分化为胰岛素分泌细胞。
