Gene Therapy Weekly

New gene therapy study findings recently were reported by researchers at University of Gottingen

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"We have studied the effects of Prox1 on the transcriptional profile of met-murine hepatocytes (MMH) obtained on embryonic day 14 (ED14). These immortalized murine hepatoblasts express numerous hepatoblast markers, but not Prox1. We have performed stable transfection with Prox1 cDNA, analyzed the transcriptome with Agilent mouse whole-genome microarrays, and validated genes by quantitative reverse transcription/polymerase chain reaction. We have observed the up-regulation of 22 genes and the down-regulation of 232 genes, by more than 12-fold. Many of these genes are involved in metabolic hepatocyte functions and may be regulated by Prox1 directly or indirectly, e.g., by the down-regulation of hepatocyte nuclear factor 4 alpha. Prox1 induces the down-regulation of transcription factors that are highly expressed in neighboring endodermal organs, suggesting a function during hepatoblast commitment. Prox1 does not influence the proliferative activity of MMH but regulates genes involved in liver morphogenesis. We have observed the up-regulation of both type-IV alpha 3 procollagen and functionally active matrix metalloproteinase-2 (MMP-2), an observation that places Prox1 at the center of liver matrix turnover. This is consistent with MMP-2 expression in hepatoblasts during liver development and with the persistence of a basal lamina around the liver bud in Prox1-deficient mice," wrote M. Papoutsi and colleagues, University of Gottingen.

The researchers concluded: "Our studies suggest that Prox1 is a multifunctional regulator of liver morphogenesis and of hepatocyte function and commitment."

Papoutsi and colleagues published their study in Cell and Tissue Research (Gene regulation by homeobox transcription factor Prox1 in murine hepatoblasts. Cell and Tissue Research, 2007;330(2):209-220).

For more information, contact J. Wilting, University of Gottingen, Center Anatomy, Dept. of Anatomy & Cell Biology, Kreuzbergring 36, D-37075 Gottingen, Germany.

Publisher contact information for the journal Cell and Tissue Research is: Springer, 233 Spring Street, New York, NY 10013, USA.

Keywords: Germany, Biotechnology, Diagnosis, Diagnostics, Enzyme Research, Gastroenterology, Gene Therapy, Hematology, Hematopoietic, Matrix Metalloproteinase, Metalloproteinases, Polymerase, Proteins, Proteomics, RNA Research, University of Gottingen.

This article was prepared by Gene Therapy Weekly editors from staff and other reports. Copyright 2008, Gene Therapy Weekly via NewsRx.com.