The Effect of Nitric Oxide on Ammonia Decomposition in Co-cultures of Hepatocytes and Hepatic Stellate Cells

Tateki Sumii, Yohei Nakano, Takuma Abe, Kazuhiro Nakashima, Toshihiro Sera, Susumu Kudo

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)

    Abstract

    Hepatic functions, such as albumin secretion and ammonia metabolism, are upregulated in response to hepatocyte growth factor (HGF) produced by hepatic stellate cells (HSC), as well as nitric oxide (NO) produced by endothelial cells under shear stress. However, the simultaneous effect of HSC and NO has not been previously investigated in a tri-co-culture model containing hepatocytes with HSC and endothelial cells under shear stress. We hypothesized that NO inhibits HGF production from HSC. To test this idea, we constructed a mono-culture model of hepatocytes and a co-culture model of hepatocytes and HSC and measured ammonia decomposition and HGF production in each model under NO load. Ammonia decomposition was significantly higher in the co-culture model under 0 ppm NO load, but no significant increase was observed under NO load. In the co-culture model, HGF was produced at 1.0 ng/mL under 0 ppm NO load and 0.3 ng/mL under NO load. Ammonia decomposition was increased by 1.0 ng/mL HGF, but not by 0.3 ng/mL HGF. These results indicated that NO inhibits HGF production from HSC; consequently, the effects of NO and co-culture with HSC cannot improve hepatic function simultaneously. Instead, the simultaneous effect of 1.0 ng/mL HGF and NO may further enhance hepatic function in vitro.

    Original languageEnglish
    Pages (from-to)625-631
    Number of pages7
    JournalIn Vitro Cellular and Developmental Biology - Animal
    Volume52
    Issue number6
    DOIs
    Publication statusPublished - Jun 1 2016

    All Science Journal Classification (ASJC) codes

    • Developmental Biology
    • Cell Biology

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