Transcription factors modulating angiotensinogen gene expression in hepatocytes

Allan R. Brasier, Junyi Li, Al Copland

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The gene encoding angiotensinogen is regulated at the transcriptional level in hepatocytes in response to glucocorticoids and inflammatory cytokines (IL-1 and TNF). These hormones activate transcription of the angiotensinogen gene by changing the abundance of NA binding proteins that interact with a multihormone-inducible enhancer located between nucleotides -615 to -440 upstream of the major transcription start site. Activation of this enhancer in hepatocytes is effected by glucocorticoid- and cytokine-inducible DNA binding proteins. Cytokine induction is mediated through the interaction of two classes of transcription factors that bind to the acute-phase response element (APRE): nuclear factor-κB (NF-κB), and CCAAT-Box/Enhancer Binding Protein (C/EBP). NF-κB is a multiprotein DNA binding complex sequestered in the cytoplasm that is induced in the nucleus by cytokines, whereas C/EBP is a nuclear transcription factor family implicated in the expression of differentiated hepatic proteins. During the acute-phase response, individual C/EBP family members are discordinately regulated: C/EBPα levels fall, whereas another C/EBP family member termed nuclear factor IL6 (NF-IL6), is induced. We investigated the interaction between the two acute-phase induced APRE-binding proteins: NF-κB and NF-IL6. Both proteins bind to overlapping nucleotides in a mutually exclusive fashion with similar affinities for the APRE. NF-IL6, a less potent transactivator, attenuates NF-κB mediated transcription late inthe evolution of the acute-phase response. These observations argue for a temporal model of sequentially-expressed transcription factors occupying the APRE during the evolution of the inflammatory process.

Original languageEnglish (US)
Pages (from-to)1564-1566
Number of pages3
JournalKidney International
Volume46
Issue number6
StatePublished - Dec 1994

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Angiotensinogen
Acute-Phase Reaction
CCAAT-Enhancer-Binding Proteins
Hepatocytes
Transcription Factors
Response Elements
Gene Expression
Cytokines
Interleukin-6
Glucocorticoids
Carrier Proteins
Nucleotides
Trans-Activators
Transcription Initiation Site
DNA-Binding Proteins
Interleukin-1
Genes
Cytoplasm
Proteins
Hormones

ASJC Scopus subject areas

  • Nephrology

Cite this

Brasier, A. R., Li, J., & Copland, A. (1994). Transcription factors modulating angiotensinogen gene expression in hepatocytes. Kidney International, 46(6), 1564-1566.

Transcription factors modulating angiotensinogen gene expression in hepatocytes. / Brasier, Allan R.; Li, Junyi; Copland, Al.

In: Kidney International, Vol. 46, No. 6, 12.1994, p. 1564-1566.

Research output: Contribution to journalArticle

Brasier, AR, Li, J & Copland, A 1994, 'Transcription factors modulating angiotensinogen gene expression in hepatocytes', Kidney International, vol. 46, no. 6, pp. 1564-1566.
Brasier, Allan R. ; Li, Junyi ; Copland, Al. / Transcription factors modulating angiotensinogen gene expression in hepatocytes. In: Kidney International. 1994 ; Vol. 46, No. 6. pp. 1564-1566.
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