Liver epithelial cells proliferate under hypoxia and protect the liver from ischemic injury via expression of HIF-1 alpha target genes.

Surgery
Yuki AbeYuzo Yamamoto

Abstract

The remnant liver after extended liver resection is susceptible to ischemic injury, resulting in the failure of liver regeneration and liver dysfunction. The present study is aimed to investigate the protective role of the liver epithelial cells (LEC), a liver progenitor cell, on hepatocytes with ischemia in vitro and in vivo. LECs were isolated from rats and cultured under hypoxic conditions (2% O(2)). The cell viability and intracellular ATP levels were measured. The activation of hypoxia-inducible factor-1α (HIF-1α) was assessed by immunofluorescence. The expression of pyruvate dehydrogenase kinase-1 (PDK-1), stromal cell-derived factor-1 (SDF-1), and chemokine receptor 4 (CXCR4) were measured. Hepatocytes were treated with SDF-1 or LEC-conditioned medium under hypoxia, and cell viability was assessed. Finally, hemorrhagic shock was induced in rats with in vivo induction of endogenous LECs, and liver damage was assessed. In LECs, but not in hepatocytes, cellular viability and intracellular ATP levels were maintained, and nuclear translocation of HIF-1α and expression of pyruvate dehydrogenase kinase-1 mRNA were increased under hypoxic culture conditions. LECs express SDF-1, and CXCR4 expression was increased in hepatocytes u...Continue Reading

References

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Citations

Mar 27, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Oihane García-IrigoyenMatias A Avila
May 27, 2015·Transplantation Reviews·Yingjia GuoYouping Li
Jun 6, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Astrid DrenckhanStephanie J Gros
Dec 26, 2013·Annals of Surgery·Kazuhiro KudohYuzo Yamamoto
Apr 21, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Cynthia JuHolger K Eltzschig

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