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首页> 外文期刊>Biochemical Pharmacology >Andrographolide promotes pancreatic duct cells differentiation into insulin-producing cells by targeting PDX-1
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Andrographolide promotes pancreatic duct cells differentiation into insulin-producing cells by targeting PDX-1

机译：Andrographolide通过靶向PDX-1将胰腺导管细胞促使胰腺导管细胞分化为产生胰岛素的细胞

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摘要

Regeneration of beta-cells by differentiation of pancreatic progenitor cells has the potential to fundamentally solve the problems of the loss of beta-cell function and mass during disease progression in both type 1 or 2 diabetes. Therefore, discovery of novel differentiation inducers to promote islet regeneration is of great significance. Pancreatic and duodenal homeobox1 (PDX-1) is a key transcription factor that promotes the development and maturation of pancreatic beta-cells. To screen potential novel small molecules for enhancing differentiation of PNAC-1 cells, a human pancreatic ductal cell lines into insulin-producing cells (IPCs), we developed a high-throughput screening method through fusing the PDX-1 promoter region with a luciferase reporter gene. We screened and identified that andrographolide named C1037 stimulates PDX-1 expression in both mRNA and protein level and significantly promotes PANC-1 cells differentiation into IPCs as compared with that of control cells. The therapeutic effect of C037 in Streptozotocin induced diabetic mouse model through differentiation of pancreatic ductal cells into insulin positive islets was also observed. Our study provides a novel method to screen compounds regulating the differentiation of pancreatic progenitor cells having the potential of enhancing islet regeneration for diabetes therapy.
机译：通过胰腺祖细胞的分化再生β细胞具有潜力，可以从根本上解决1或2型糖尿病患者疾病进展期间β细胞功能和质量的问题。因此，发现新型分化诱导剂以促进胰岛再生具有重要意义。胰腺和十二指肠Homeobox1（PDX-1）是促进胰腺β细胞的发育和成熟的关键转录因素。为了筛选用于增强PNAC-1细胞分化的潜在新型小分子，将人胰腺导管细胞系进入胰岛素的细胞（IPC），我们通过用荧光素酶报告者融合PDX-1启动子区，开发了一种高通量筛选方法基因。我们筛选并鉴定了名为C1037的Andrographolide刺激MRNA和蛋白质水平中的PDX-1表达，与对照细胞相比，显着促进Panc-1细胞分化为IPC。还观察到通过将胰腺导管细胞分化到胰岛素阳性胰岛中的链脲佐菌素诱导糖尿病小鼠模型中CO 37诱导的糖尿病小鼠模型的治疗效果。我们的研究提供了一种新的方法，用于筛选调节胰腺祖细胞分化具有增强糖尿病疗法的胰岛再生的胰腺祖细胞的分化的化合物。

著录项

  • 来源
    《Biochemical Pharmacology》 |2020年第1期|共13页
  • 作者

    Zhang Shengmei; Huang Feirong; Tian Wenjin; Lai Jiashuang; Qian Lixia; Hong Wanjin; Chen Haifeng; Li Liang-cheng;

  • 作者单位

    Xiamen Univ Sch Pharmaceut Sci State Key Lab Cellular Stress Biol Fujian Prov Key Lab Innovat;

    Xiamen Univ Sch Pharmaceut Sci State Key Lab Cellular Stress Biol Fujian Prov Key Lab Innovat;

    Xiamen Univ Sch Pharmaceut Sci State Key Lab Cellular Stress Biol Fujian Prov Key Lab Innovat;

    Xiamen Univ Sch Pharmaceut Sci State Key Lab Cellular Stress Biol Fujian Prov Key Lab Innovat;

    Xiamen Univ Sch Pharmaceut Sci State Key Lab Cellular Stress Biol Fujian Prov Key Lab Innovat;

    Xiamen Univ Sch Pharmaceut Sci State Key Lab Cellular Stress Biol Fujian Prov Key Lab Innovat;

    Xiamen Univ Sch Pharmaceut Sci State Key Lab Cellular Stress Biol Fujian Prov Key Lab Innovat;

    Xiamen Univ Sch Pharmaceut Sci State Key Lab Cellular Stress Biol Fujian Prov Key Lab Innovat;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

    Pancreatic duct cells; PDX-1; Islet regeneration; Differentiation; Andrographolide;

    机译：胰管细胞;PDX-1;胰岛再生;分化;andrographolide;

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