In vitro transformation of adult rat hepatic progenitor cells into pancreatic endocrine hormone‐producing cells View Full Text


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Article Info

DATE

2008-05

AUTHORS

Hiroyuki Kawasaki, Toru Mizuguchi, Yamato Kikkawa, Hideki Oshima, Yasushi Sasaki, Takashi Tokino, Yasuo Kokai, Jun‐Ichi Miyazaki, Tadashi Katsuramaki, Toshihiro Mitaka, Koichi Hirata

ABSTRACT

BACKGROUND/PURPOSE: Pancreatic and duodenal homeobox factor 1 (Pdx-1) plays an important role in initiating differentiation toward pancreatic endocrine cells. The transdifferentiation or transformation of hepatocytes into pancreatic endocrine cells could be feasible, due to their similar cellular origins. Our goal in this study was to see if small hepatocytes (SHs) could give rise to pancreatic endocrine cells via exogenous Pdx-1 gene expression. METHODS: SHs were cultured for 10 days before adenovirus (Adt)-mediated Pdx-1 gene transfection. We performed western blot analysis for pancreatic transcription factors in the nuclei and reverse-transcription polymerase chain reaction (RT-PCR) for the gene expression of pancreatic endocrine hormones. Confocal laser microscanning analysis was used to observe the transformation of SHs. RESULTS: Pancreatic transcription factors such as Pdx-1, Ngn3, NeuroD, Nkx2.2, and Pax6 were induced after Adt-Pdx-1 gene transfection. The mRNA expression of pancreatic endocrine hormones (insulin, glucagon, and somatostatin) was induced after the gene transfection. Pdx-1 was expressed in the nucleus, where the cells were positive for one or more of the hormones and cytokeratin (CK) 8. Some cells were positive for multiple hormones. The insulin level increased while the glucagon level decreased after the glucose loading test, depending on the glucose concentration. CONCLUSIONS: SHs are transformed into functional pancreatic endocrine cells after Pdx-1 gene transfection. More... »

PAGES

310-317

References to SciGraph publications

  • 2005-06-01. Pancreatic differentiation in JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
  • 2003-01-01. β-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas in GENE THERAPY
  • 2005-06-01. Stem‐cell therapy for hepatobiliary pancreatic disease in JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
  • 2005-06-01. Regenerative medicine of the pancreatic β cells in JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
  • 2002-07. Regulatory phases of early liver development: paradigms of organogenesis in NATURE REVIEWS GENETICS
  • 2000-05. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia in NATURE MEDICINE
  • 2005-10-01. Hepatocyte transplantation for total liver repopulation in JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00534-007-1252-3

    DOI

    http://dx.doi.org/10.1007/s00534-007-1252-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010921671

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18535770


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    33 schema:description BACKGROUND/PURPOSE: Pancreatic and duodenal homeobox factor 1 (Pdx-1) plays an important role in initiating differentiation toward pancreatic endocrine cells. The transdifferentiation or transformation of hepatocytes into pancreatic endocrine cells could be feasible, due to their similar cellular origins. Our goal in this study was to see if small hepatocytes (SHs) could give rise to pancreatic endocrine cells via exogenous Pdx-1 gene expression. METHODS: SHs were cultured for 10 days before adenovirus (Adt)-mediated Pdx-1 gene transfection. We performed western blot analysis for pancreatic transcription factors in the nuclei and reverse-transcription polymerase chain reaction (RT-PCR) for the gene expression of pancreatic endocrine hormones. Confocal laser microscanning analysis was used to observe the transformation of SHs. RESULTS: Pancreatic transcription factors such as Pdx-1, Ngn3, NeuroD, Nkx2.2, and Pax6 were induced after Adt-Pdx-1 gene transfection. The mRNA expression of pancreatic endocrine hormones (insulin, glucagon, and somatostatin) was induced after the gene transfection. Pdx-1 was expressed in the nucleus, where the cells were positive for one or more of the hormones and cytokeratin (CK) 8. Some cells were positive for multiple hormones. The insulin level increased while the glucagon level decreased after the glucose loading test, depending on the glucose concentration. CONCLUSIONS: SHs are transformed into functional pancreatic endocrine cells after Pdx-1 gene transfection.
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