Logo image
Back
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
Journal article   Open access   Peer reviewed

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

M Zaiou, N Azrolan, T Hayek, H Wang, L Wu, M Haghpassand, B Cizman, M P Madaio, J Milbrandt, J B Marsh, …
The Journal of clinical investigation, v 101(8), pp 1699-1707
15 Apr 1998
DOI: https://doi.org/10.1172/JCI2166
PMID: 9541501
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1172/jci2166View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open
url
https://doi.org/10.1172/JCI2166View
Published, Version of Record (VoR) Open

Abstract

Animals Apolipoprotein A-I - blood Apolipoprotein A-I - genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Cholesterol, HDL - blood Disease Models, Animal DNA-Binding Proteins - genetics Early Growth Response Protein 1 Gene Expression Hepatocyte Nuclear Factor 4 Humans Immediate-Early Proteins Liver - metabolism Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Knockout Mice, Transgenic Nephrotic Syndrome - blood Nephrotic Syndrome - genetics Nephrotic Syndrome - metabolism Phosphoproteins - genetics Promoter Regions, Genetic RNA, Messenger - genetics RNA, Messenger - metabolism Transcription Factors - genetics
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 HDL-C, apo A-I, and hepatic apo A-I mRNA were lowest in nonnephrotic EGR1-KO mice and highest in nephrotic mice expressing EGR-1. Although in EGR1-KO mice HDL-C, apo A-I, and apo A-I mRNA levels also increased after NTS injection, they were approximately half of those in the nephrotic EGR-1-expressing mice. We conclude that in this model, basal and induced apo A-I gene expression in vivo are regulated by the trans-acting factor EGR-1 and require the same cis-acting elements in the core promoter.

Metrics

5 Record Views
24 citations in Web of Science
24 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Industry collaboration
Domestic collaboration
Web of Science research areas
Medicine, Research & Experimental
Logo image