The full induction of human apoprotein A-I gene expression by the experimental nephrotic syndrome in transgenic mice depends on cis-acting elements in the proximal 256 base-pair promoter region and the trans-acting factor early growth response factor 1

The Journal of Clinical Investigation
M ZaiouE A Fisher

Abstract

To identify molecular factors regulating apo A-I production in vivo, we induced in transgenic mice the experimental nephrotic syndrome, which results in elevated levels of HDL cholesterol (HDL-C), plasma apo A-I, and hepatic apo A-I mRNA. Human (h) apo A-I transgenic mice with different length 5' flanking sequences (5.5 or 0.256 kb, the core promoter for hepatic-specific basal expression) were injected with nephrotoxic (NTS) or control serum. With nephrosis, there were comparable (greater than twofold) increases in both lines of HDL-C, h-apo A-I, and hepatic h-apo A-I mRNA, suggesting that cis-acting elements regulating induced apo A-I gene expression were within its core promoter. Hepatic nuclear extracts from control and nephrotic mice footprinted the core promoter similarly, implying that the same elements regulated basal and induced expression. Hepatic mRNA levels for hepatocyte nuclear factor (HNF) 4 and early growth response factor (EGR) 1, trans-acting factors that bind to the core promoter, were measured: HNF4 mRNA was not affected, but that of EGR-1 was elevated approximately fivefold in the nephrotic group. EGR-1 knockout (EGR1-KO) mice or mice expressing EGR-1 were injected with either NTS or control serum. Levels of...Continue Reading

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Citations

Apr 8, 2006·American Journal of Respiratory Cell and Molecular Biology·Paul R ReynoldsJohn R Hoidal
Nov 12, 2005·American Journal of Nephrology·Michael P MadaioDavid L Gasser
Oct 18, 2003·Journal of Lipid Research·Stefania Lamon-Fava, Dale Micherone
Apr 9, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Paul R ReynoldsJohn R Hoidal
Jun 30, 2001·Canadian Journal of Physiology and Pharmacology·N SaadaneL E Chalifour
Jul 11, 2002·American Journal of Physiology. Cell Physiology·Libin CuiK Y Lei
Mar 27, 2001·Current Opinion in Lipidology·V I ZannisD Kardassis
Jul 1, 2006·American Journal of Respiratory Cell and Molecular Biology·Charles ThompsonMarek Rola-Pleszczynski
Feb 19, 2011·American Journal of Respiratory Cell and Molecular Biology·Dane Parker, Alice Prince
Mar 18, 1999·The American Journal of Pathology·E S Silverman, T Collins
Oct 6, 2000·The American Journal of Pathology·W ZhangS F Yan

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