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Andrographolide promotes pancreatic duct cells differentiation into insulin-producing cells by targeting PDX-1.
Biochem Pharmacol. 2020 04; 174:113785.BP

Abstract

Regeneration of β-cells by differentiation of pancreatic progenitor cells has the potential to fundamentally solve the problems of the loss of β-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 β-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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Zhang S
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
Huang F
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
Tian W
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
Lai J
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
Qian L
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
Hong W
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China. Electronic address: mcbhwj@imcb.a-star.edu.sg.
Chen H
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China. Electronic address: haifeng@xmu.edu.cn.
Li LC
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China. Electronic address: lchli2013@xmu.edu.cn.

MeSH

AndrographisAnimalsCell Culture TechniquesCell DifferentiationCell LineDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1DiterpenesGene ExpressionGlucose Tolerance TestHomeodomain ProteinsHumansHypoglycemic AgentsInsulin SecretionInsulin-Secreting CellsMaleMicePancreatic DuctsTrans-Activators

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31887289

Citation

Zhang, Shengmei, et al. "Andrographolide Promotes Pancreatic Duct Cells Differentiation Into Insulin-producing Cells By Targeting PDX-1." Biochemical Pharmacology, vol. 174, 2020, p. 113785.
Zhang S, Huang F, Tian W, et al. Andrographolide promotes pancreatic duct cells differentiation into insulin-producing cells by targeting PDX-1. Biochem Pharmacol. 2020;174:113785.
Zhang, S., Huang, F., Tian, W., Lai, J., Qian, L., Hong, W., Chen, H., & Li, L. C. (2020). Andrographolide promotes pancreatic duct cells differentiation into insulin-producing cells by targeting PDX-1. Biochemical Pharmacology, 174, 113785. https://doi.org/10.1016/j.bcp.2019.113785
Zhang S, et al. Andrographolide Promotes Pancreatic Duct Cells Differentiation Into Insulin-producing Cells By Targeting PDX-1. Biochem Pharmacol. 2020;174:113785. PubMed PMID: 31887289.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Andrographolide promotes pancreatic duct cells differentiation into insulin-producing cells by targeting PDX-1. AU - Zhang,Shengmei, AU - Huang,Feirong, AU - Tian,Wenjin, AU - Lai,Jiashuang, AU - Qian,Lixia, AU - Hong,Wanjin, AU - Chen,Haifeng, AU - Li,Liang-Cheng, Y1 - 2019/12/28/ PY - 2019/10/29/received PY - 2019/12/23/accepted PY - 2019/12/31/pubmed PY - 2020/8/25/medline PY - 2019/12/31/entrez KW - Andrographolide KW - Differentiation KW - Islet regeneration KW - PDX-1 KW - Pancreatic duct cells SP - 113785 EP - 113785 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 174 N2 - Regeneration of β-cells by differentiation of pancreatic progenitor cells has the potential to fundamentally solve the problems of the loss of β-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 β-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. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/31887289/Andrographolide_promotes_pancreatic_duct_cells_differentiation_into_insulin_producing_cells_by_targeting_PDX_1_ DB - PRIME DP - Unbound Medicine ER -