title: The Effect of Nitric Oxide on Ammonia Decomposition in Co-cultures of Hepatocytes and Hepatic Stellate Cells.
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.
authors.affiliation: Department of Mechanical Engineering, Graduate school of Mechanical Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan. sumii.t.377@s.kyushu-u.ac.jp.
authors.forename: Tateki
authors.initials: T
authors.lastname: Sumii
authors.affiliation: Department of Mechanical Engineering, Graduate school of Mechanical Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Department of Mechanical Engineering, Graduate school of Mechanical Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Mechanical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Department of Mechanical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sera
authors.affiliation: Department of Mechanical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kudo
mesh_terms: D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats
chemical_list: D009569:Nitric Oxide; D017228:Hepatocyte Growth Factor; D000641:Ammonia
keywords: Co-culture; Hepatic stellate cells; Hepatocyte growth factor; Hepatocytes; Nitric oxide