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

研究成果: Article査読

13 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)385-393
ページ数9
ジャーナルMicrocirculation
20
5
DOI
出版ステータスPublished - 2013 7

ASJC Scopus subject areas

  • 生理学
  • 分子生物学
  • 循環器および心血管医学
  • 生理学(医学)

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