title: Pyrroloquinoline-quinone suppresses liver fibrogenesis in mice.
abstract: Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injuries, and its progression toward cirrhosis is the major cause of liver-related morbidity and mortality worldwide. However, anti-fibrotic treatment remains an unconquered area for drug development. Accumulating evidence indicate that oxidative stress plays a critical role in liver fibrogenesis. In this study, we found that PQQ, a natural anti-oxidant present in a wide variety of human foods, exerted potent anti-fibrotic and ROS-scavenging activity in Balb/C mouse models of liver fibrosis. The antioxidant activity of PQQ was involved in the modulation of multiple steps during liver fibrogenesis, including chronic liver injury, hepatic inflammation, as well as activation of hepatic stellate cells and production of extracellular matrix. PQQ also suppressed the up-regulation of RACK1 in activated HSCs in vivo and in vitro. Our data suggest that PQQ suppresses oxidative stress and liver fibrogenesis in mice, and provide rationale for the clinical application of PQQ in the prevention and treatment of liver fibrosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R.China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Jia
authors.affiliation: Institute of Biomedical Science, Fudan University, Shanghai, P.R.China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Duan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R.China.
authors.forename: Peike
authors.initials: P
authors.lastname: Peng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R.China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R.China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R.China; Institute of Biomedical Science, Fudan University, Shanghai, P.R.China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009479:Neuropeptides / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D045542:PQQ Cofactor / Q000494:pharmacology*; D000075370:Receptors for Activated C Kinase; D013853:Thioacetamide / Q000633:toxicity
chemical_list: D000975:Antioxidants; D016207:Cytokines; D009479:Neuropeptides; C090294:RACK1 protein, mouse; D000075370:Receptors for Activated C Kinase; D013853:Thioacetamide; D045542:PQQ Cofactor
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