Transcriptional regulation of hepatic angiotensinogen gene expression by the acute-phase response.
The acute-phase response is a protective physiological reaction to tissue injury manifested by the immediate increase in production and secretion of liver proteins the function of which is to re-establish the homeostasis altered by injury. Such proteins include blood coagulation factors, opsonins, protease-inhibitors and angiotensinogen, a precursor of the potent vasopressor peptide angiotensin II. The angiotensinogen gene is typical of genes regulated during the acute-phase response inasmuch as the promoter regulating its transcription rate is acutely responsive to three known mediators of the acute-phase response: glucocorticoids, and the cytokines interleukin-1 and tumor necrosis factor. We present a model, based on experimental evidence, for the mechanism by which angiotensinogen gene transcription is regulated in a graded fashion by the interplay of several hormonally-inducible transcription factors that bind a hormonally-inducible enhancer unit of the angiotensinogen promoter. These factors include the glucocorticoid receptor, nuclear factor kappa B and members of the CAAT/viral enhancer (C/EBP) family of DNA-binding proteins.
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Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston 02114.
Brasier
A R
AR
Habener
J F
JF
D000210:Acute-Phase Reaction / Q000378:metabolism*; D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005796:Genes; D005938:Glucocorticoids; D007375:Interleukin-1; D008099:Liver / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
D005938:Glucocorticoids; D007375:Interleukin-1; D016328:NF-kappa B; D000808:Angiotensinogen