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Pdx-1 or Pdx-1-VP16 protein transduction induces beta-cell gene expression in liver-stem WB cells.

Authors: Delisle, JC  Martignat, L  Dubreil, L  Sai, P  Bach, JM  Louzier, V  Bosch, S 
Citation: Delisle JC, etal., BMC Res Notes. 2009 Jan 9;2:3.
Pubmed: (View Article at PubMed) PMID:19134185
DOI: Full-text: DOI:10.1186/1756-0500-2-3

ABSTRACT: BACKGROUND: Pancreatic duodenal homeobox-1 (Pdx-1) or Pdx-1-VP16 gene transfer has been shown to induce in vitro rat liver-stem WB cell conversion into pancreatic endocrine precursor cells. High glucose conditions were necessary for further differentiation into functional insulin-producing cells. Pdx-1 has the ability to permeate different cell types due to an inherent protein transduction domain (PTD). In this study, we evaluated liver-to-pancreas conversion of WB cells following Pdx-1 or Pdx-1-VP16 protein transduction. FINDINGS: WB cells were grown in high glucose medium containing Pdx-1 or Pdx-1-VP16 recombinant proteins for two weeks. beta-like cell commitment was analysed by RT-PCR of pancreatic endocrine genes. We found that WB cells in high glucose culture spontaneously express pancreatic endocrine genes (Pdx-1, Ngn3, Nkx2.2, Kir6.2). Their further differentiation into beta-like cells expressing genes related to endocrine pancreas development (Ngn3, NeuroD, Pax4, Nkx2.2, Nkx6.1, Pdx-1) and beta-cell function (Glut-2, Kir6.2, insulin) was achieved only in the presence of Pdx-1(-VP16) protein. CONCLUSION: These results demonstrate that Pdx-1(-VP16) protein transduction is instrumental for in vitro liver-to-pancreas conversion and is an alternative to gene therapy for beta-cell engineering for diabetes cell therapy.

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CRRD Object Information
CRRD ID: 2306238
Created: 2009-03-27
Species: All species
Last Modified: 2009-03-27
Status: ACTIVE



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