Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
HIF-2α, but not HIF-1α, promotes iron absorption in mice
Maria Mastrogiannaki, … , Sophie Vaulont, Carole Peyssonnaux
Maria Mastrogiannaki, … , Sophie Vaulont, Carole Peyssonnaux
Published April 6, 2009
Citation Information: J Clin Invest. 2009;119(5):1159-1166. https://doi.org/10.1172/JCI38499.
View: Text | PDF
Research Article Gastroenterology Article has an altmetric score of 7

HIF-2α, but not HIF-1α, promotes iron absorption in mice

  • Text
  • PDF
Abstract

HIF transcription factors (HIF-1 and HIF-2) are central mediators of cellular adaptation to hypoxia. Because the resting partial pressure of oxygen is low in the intestinal lumen, epithelial cells are believed to be mildly hypoxic. Having recently established a link between HIF and the iron-regulatory hormone hepcidin, we hypothesized that HIFs, stabilized in the hypoxic intestinal epithelium, may also play critical roles in regulating intestinal iron absorption. To explore this idea, we first established that the mouse duodenum, the site of iron absorption in the intestine, is hypoxic and generated conditional knockout mice that lacked either Hif1a or Hif2a specifically in the intestinal epithelium. Using these mice, we found that HIF-1α was not necessary for iron absorption, whereas HIF-2α played a crucial role in maintaining iron balance in the organism by directly regulating the transcription of the gene encoding divalent metal transporter 1 (DMT1), the principal intestinal iron transporter. Specific deletion of Hif2a led to a decrease in serum and liver iron levels and a marked decrease in liver hepcidin expression, indicating the involvement of an induced systemic response to counteract the iron deficiency. This finding may provide a basis for the development of new strategies, specifically in targeting HIF-2α, to improve iron homeostasis in patients with iron disorders.

Authors

Maria Mastrogiannaki, Pavle Matak, Brian Keith, M. Celeste Simon, Sophie Vaulont, Carole Peyssonnaux

×

Figure 4

Decrease in serum and liver iron and increase in serum EPO levels in intestine-specific Hif2a-knockout mice.

Options: View larger image (or click on image) Download as PowerPoint
Decrease in serum and liver iron and increase in serum EPO levels in int...
(A) Quantification of serum and liver iron levels in vil-Cre+/HIF-1αfl/fl and vil-Cre+/HIF-2αfl/fl mice and WT littermates (n = 6 in each group). (B) Serum EPO levels in vil-Cre+/HIF-1αfl/fl and vil-Cre+/HIF-2αfl/fl mice and WT littermates. *P < 0.05, ***P < 0.001, unpaired Student’s t test.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 1 patents
Highlighted by 1 platforms
Referenced in 1 clinical guideline sources
184 readers on Mendeley
5 readers on CiteULike
See more details