Hypoxia-inducible factor-1 is a determinant of lobular structure and oxygen consumption in the liver

Kosuke Tsukada, Toshihide Tajima, Shutaro Hori, Tomomi Matsuura, Randall S. Johnson, Nobuhito Goda, Makoto Suematsu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objective: Hypoxia-inducible factor is a hypoxia-responsive transcriptional factor that controls the expression of proteins contributing to homeostatic responses to hypoxia. Spatial heterogeneity of tissue oxygenation has been postulated as a determinant of structure and function of hepatic lobules, although its molecular mechanisms remain unknown. This study aimed to examine the role of HIF-1 expressed in hepatocytes in regulation of hepatic microcirculation. Methods: We have generated mice harboring a floxed HIF-1α allele, and employed the albumin-Cre transgenic line to inactivate the gene site-specifically in hepatocytes. Results: Intravital observation of the hepatic microcirculation revealed extension of hepatic lobules in HIF-1α-deficient mice. Measurement of microvascular diameter, velocity, and local oxygen tension by laser-assisted phosphorimetry showed that the oxygen consumption in the lobules of HIF-1α-deficient mice was greater than that in those of control mice. Isolated hepatocytes from HIF-1α-deficient mice also stimulated oxygen consumptions with increased contents of mtDNA. Overexpression of HIF-1α decreased the expression of PGC-1α mRNA, whereas the knockdown of the HIF-1α gene increased it, suggesting that HIF-1 regulates cellular respiration through mitochondrial biogenesis. Conclusions: Our results suggest that constitutive expression of HIF-1α in hepatocytes acts as a determinant of hepatic lobular structure and oxygen consumption by changing mitochondrial contents.

Original languageEnglish
Pages (from-to)385-393
Number of pages9
JournalMicrocirculation
Volume20
Issue number5
DOIs
Publication statusPublished - 2013 Jul
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Oxygen Consumption
Hepatocytes
Liver
Microcirculation
Cell Respiration
Organelle Biogenesis
Mitochondrial DNA
Genes
Albumins
Lasers
Alleles
Observation
Oxygen
Messenger RNA
Hypoxia
Proteins

Keywords

  • HIF-1α
  • Liver
  • Mitochondrial biogenesis
  • Oxygen consumption

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Tsukada, K., Tajima, T., Hori, S., Matsuura, T., Johnson, R. S., Goda, N., & Suematsu, M. (2013). Hypoxia-inducible factor-1 is a determinant of lobular structure and oxygen consumption in the liver. Microcirculation, 20(5), 385-393. https://doi.org/10.1111/micc.12033

Hypoxia-inducible factor-1 is a determinant of lobular structure and oxygen consumption in the liver. / Tsukada, Kosuke; Tajima, Toshihide; Hori, Shutaro; Matsuura, Tomomi; Johnson, Randall S.; Goda, Nobuhito; Suematsu, Makoto.

In: Microcirculation, Vol. 20, No. 5, 07.2013, p. 385-393.

Research output: Contribution to journalArticle

Tsukada, K, Tajima, T, Hori, S, Matsuura, T, Johnson, RS, Goda, N & Suematsu, M 2013, 'Hypoxia-inducible factor-1 is a determinant of lobular structure and oxygen consumption in the liver', Microcirculation, vol. 20, no. 5, pp. 385-393. https://doi.org/10.1111/micc.12033
Tsukada, Kosuke ; Tajima, Toshihide ; Hori, Shutaro ; Matsuura, Tomomi ; Johnson, Randall S. ; Goda, Nobuhito ; Suematsu, Makoto. / Hypoxia-inducible factor-1 is a determinant of lobular structure and oxygen consumption in the liver. In: Microcirculation. 2013 ; Vol. 20, No. 5. pp. 385-393.
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