Antisense oligonucleotides to differentiation-specific element binding protein (DSEB) mRNA inhibit adipocyte differentiation

Biochemical and Biophysical Research Communications
R E LyleR E McGehee

Abstract

The Differentiation-Specific Element Binding Protein (DSEB) was identified by binding to a specific cis-acting DNA element (DSE) responsible for the irreversible continued expression of the angiotensinogen gene after differentiation of 3T3-L1 adipoblasts to adipocytes. It was also identified as the large subunit of the Replication Factor C complex. During 3T3-L1 adipoblast differentiation, DSEB is induced early and interacts with the DSE that is essential for the sustained transcriptional activation of the angiotensinogen gene. Here we describe loss of function studies in 3T3-L1 cells performed with antisense phosphorothioate oligonucleotides that hybridize to DSEB mRNA. Treatment with 15, 25, and 50 microM antisense DSEB resulted in a dose-dependent inhibition of differentiation-specific lipid accumulation after 3 days of hormonal stimulation. Similar treatment also markedly reduced differentiation-dependent expression of mRNAs encoding angiotensinogen and the fat-specific fatty acid binding protein, aP2. Further, 50 microM antisense DSEB treatment resulted in a significant approximately 50% inhibition of the cell proliferation that occurs early in 3T3-L1 adipogenesis. Control experiments using the DSEB sense oligonucleotide h...Continue Reading

Citations

Oct 1, 2016·Molecular Metabolism·Zulaykho ShamansurovaJulie L Lavoie
Jul 15, 1999·Journal of Hypertension·S EngeliA M Sharma
Mar 1, 2003·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·G H GoossensM A van Baak
Apr 5, 2003·The International Journal of Biochemistry & Cell Biology·Stefan EngeliArya M Sharma

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