Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2005; 11(15): 2277-2282
Published online Apr 21, 2005. doi: 10.3748/wjg.v11.i15.2277
Heterogeneity in predisposition of hepatic cells to be induced into pancreatic endocrine cells by PDX-1
Shun Lu, Wei-Ping Wang, Xiao-Fei Wang, Zong-Mei Zheng, Ping Chen, Kang-Tao Ma, Chun-Yan Zhou
Shun Lu, Wei-Ping Wang, Xiao-Fei Wang, Ping Chen, Kang-Tao Ma, Chun-Yan Zhou, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing 100083, China
Zong-Mei Zheng, Peking University Stem Cell Research Center, Beijing 100083, China
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No. 30240087; the National High Technology Research and Development Program of China, No. 2003AA205090
Correspondence to: Professor Chun-Yan Zhou, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, 38 Xue Yuan Road, Haidian District, Beijing 100083, China. chunyanzhou@bjmu.edu.cn
Telephone: +86-10-82802417 Fax: +86-10-62015582
Received: May 12, 2004
Revised: May 13, 2004
Accepted: June 24, 2004
Published online: April 21, 2005
Abstract

AIM: The role of Pancreatic and Duodenal Homeobox-1 (PDX-1) as a major regulator of pancreatic development determines the function and phenotype of β cell. In this study, potential plasticity of liver cells into pancreatic endocrine cells induced by PDX-1 was evaluated.

METHODS: Human hepatoma cell line HepG2 was stably transfected with mammalian expression plasmid pcDNA3-PDX encoding human PDX-1 gene. Ectopic expression of PDX-1 and insulin were detected by RT-PCR, Western blot and/or immunostaining. PDX-1+ HepG2 cells were transplanted under renal capsule of STZ-induced diabetic nude mice (n = 16) to examine the inducing effect in vivo.

RESULTS: Exogenous PDX-1 transgene was proved to express effectively in HepG2 cell at both mRNA and protein levels. The expression of endogenous insulin and some β cell-specific differentiation markers and transcription factors were not induced in PDX-1+ HepG2 cells. When transplanted under renal capsule of STZ-induced diabetic nude mice, PDX-1+ HepG2 cells did not generate insulin-producing cells. These data indicated that stable transfected PDX-1 could not convert hepatoma cell line HepG2 to pancreatic cells in vitro or in vivo. Mature hepatocytes might need much more complicated or rigorous conditions to be shifted to insulin-producing cells.

CONCLUSION: The expression of exogenous PDX-1 is not sufficient to induce relatively mature hepatocytes differentiating into insulin-producing cells.

Keywords: PDX-1, HepG2, Insulin, Transgene, Diabetes