Ectopically expressed PDX-1 in liver initiates endocrine and exocrine pancreas differentiation but causes dysmorphogenesis - PubMed (original) (raw)

. 2003 Oct 24;310(3):1017-25.

doi: 10.1016/j.bbrc.2003.09.108.

H Kaneto, Y Kajimoto, S Hirota, Y Arakawa, Y Fujitani, Y Umayahara, H Watada, Y Yamasaki, M A Magnuson, J Miyazaki, M Hori

Affiliations

• PMID: 14550306
• DOI: 10.1016/j.bbrc.2003.09.108

Ectopically expressed PDX-1 in liver initiates endocrine and exocrine pancreas differentiation but causes dysmorphogenesis

T Miyatsuka et al. Biochem Biophys Res Commun. 2003.

Abstract

To date, the potency of pancreatic and duodenal homeobox gene 1 (PDX-1) in inducing differentiation into insulin-producing cells has been demonstrated in some cells and tissues. In order to carry out efficient screening of somatic tissues and cells that can transdifferentiate into beta-cell-like cells in response to PDX-1, we generated CAG-CAT-PDX1 transgenic mice carrying a transgene cassette composed of the chicken beta-actin gene (CAG) promoter and a floxed stuffer DNA sequence (CAT) linked to PDX-1 cDNA. When the mice were crossed with Alb-Cre mice, which express the Cre recombinase driven by the rat albumin gene promoter, PDX-1 was expressed in more than 50% of hepatocytes and cholangiocytes. The PDX-1 (+) livers expressed a variety of endocrine hormone genes such as insulin, glucagon, somatostatin, and pancreatic polypeptide. In addition, they expressed exocrine genes such as elastase-1 and chymotrypsinogen 1B. However, the mice exhibited marked jaundice due to conjugated hyperbilirubinemia, and the liver tissue displayed abnormal lobe structures and multiple cystic lesions. Thus, the in vivo ectopic expression of PDX-1 in albumin-producing cells was able to initiate but not complete the differentiation of liver cells into pancreatic cells. The conditional PDX-1 transgenic mouse system developed in this study appeared to be useful for efficient screening of PDX-1 responsive somatic tissues and cells.

PubMed Disclaimer

Similar articles

• Improved glucose tolerance and acinar dysmorphogenesis by targeted expression of transcription factor PDX-1 to the exocrine pancreas.
  Heller RS, Stoffers DA, Bock T, Svenstrup K, Jensen J, Horn T, Miller CP, Habener JF, Madsen OD, Serup P. Heller RS, et al. Diabetes. 2001 Jul;50(7):1553-61. doi: 10.2337/diabetes.50.7.1553. Diabetes. 2001. PMID: 11423476
• The Tet-On system in transgenic mice: inhibition of the mouse pdx-1 gene activity by antisense RNA expression in pancreatic beta-cells.
  Lottmann H, Vanselow J, Hessabi B, Walther R. Lottmann H, et al. J Mol Med (Berl). 2001 Jun;79(5-6):321-8. doi: 10.1007/s001090100229. J Mol Med (Berl). 2001. PMID: 11485027
• Rat endocrine pancreatic development in relation to two homeobox gene products (Pdx-1 and Nkx 6.1).
  Oster A, Jensen J, Serup P, Galante P, Madsen OD, Larsson LI. Oster A, et al. J Histochem Cytochem. 1998 Jun;46(6):707-15. doi: 10.1177/002215549804600602. J Histochem Cytochem. 1998. PMID: 9603781
• PDX-1 and the pancreas.
  Ashizawa S, Brunicardi FC, Wang XP. Ashizawa S, et al. Pancreas. 2004 Mar;28(2):109-20. doi: 10.1097/00006676-200403000-00001. Pancreas. 2004. PMID: 15028942 Review.
• Crucial role of PDX-1 in pancreas development, beta-cell differentiation, and induction of surrogate beta-cells.
  Kaneto H, Miyatsuka T, Shiraiwa T, Yamamoto K, Kato K, Fujitani Y, Matsuoka TA. Kaneto H, et al. Curr Med Chem. 2007;14(16):1745-52. doi: 10.2174/092986707781058887. Curr Med Chem. 2007. PMID: 17627512 Review.

Cited by

• Direct Reprogramming of Somatic Cells into Induced β-Cells: An Overview.
  Narayan G, Ronima K R, Thummer RP. Narayan G, et al. Adv Exp Med Biol. 2023;1410:171-189. doi: 10.1007/5584_2022_756. Adv Exp Med Biol. 2023. PMID: 36515866
• STAT3 suppression and β-cell ablation enhance α-to-β reprogramming mediated by Pdx1.
  Wakabayashi Y, Miyatsuka T, Miura M, Himuro M, Taguchi T, Iida H, Nishida Y, Fujitani Y, Watada H. Wakabayashi Y, et al. Sci Rep. 2022 Dec 10;12(1):21419. doi: 10.1038/s41598-022-25941-5. Sci Rep. 2022. PMID: 36496541 Free PMC article.
• Reprogramming-Evolving Path to Functional Surrogate β-Cells.
  Kalo E, Read S, Ahlenstiel G. Kalo E, et al. Cells. 2022 Sep 8;11(18):2813. doi: 10.3390/cells11182813. Cells. 2022. PMID: 36139388 Free PMC article. Review.
• Direct Reprogramming of Different Cell Lineages into Pancreatic β-Like Cells.
  Colarusso JL, Zhou Q. Colarusso JL, et al. Cell Reprogram. 2022 Oct;24(5):252-258. doi: 10.1089/cell.2022.0048. Epub 2022 Jul 15. Cell Reprogram. 2022. PMID: 35838597 Free PMC article. Review.
• Molecular mechanisms of transcription factor mediated cell reprogramming: conversion of liver to pancreas.
  Wild SL, Tosh D. Wild SL, et al. Biochem Soc Trans. 2021 Apr 30;49(2):579-590. doi: 10.1042/BST20200219. Biochem Soc Trans. 2021. PMID: 33666218 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal