title: Cu,Zn-SOD deficiency induces the accumulation of hepatic collagen.
abstract: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic diseases, and results in the development of fibrosis. Oxidative stress is thought to be one of the underlying causes of NAFLD. Copper/zinc superoxide dismutase (SOD1) is a primary antioxidative enzyme that scavenges superoxide anion radicals. Although SOD1 knockout (KO) mice have been reported to develop fatty livers, it is not known whether this lack of SOD1 leads to the development of fibrosis. Since the accumulation of collagen typically precedes liver fibrosis, we assessed the balance between the synthesis and degradation of collagen in liver tissue from SOD1 KO mice. We found a higher accumulation of collagen in the livers of SOD1 KO mice compared to wild type mice. The level of expression of HSP47, a chaperone of collagen, and a tissue inhibitor (TIMP1) of matrix metalloproteinases (a collagen degradating enzyme) was also increased in SOD1 KO mice livers. These results indicate that collagen synthesis is increased but that its degradation is inhibited in SOD1 KO mice livers. Moreover, SOD1 KO mice liver sections were extensively modified by advanced glycation end products (AGEs), which suggest that collagen in SOD1 KO mice liver might be also modified with AGEs and then would be more resistant to the action of collagen degrading enzymes. These findings clearly show that oxidative stress plays an important role in the progression of liver fibrosis.
authors.affiliation: a Department of Biochemistry, Hyogo College of Medicine , Nishinomiya , Hyogo , Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sakiyama
authors.affiliation: a Department of Biochemistry, Hyogo College of Medicine , Nishinomiya , Hyogo , Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Fujiwara
authors.affiliation: a Department of Biochemistry, Hyogo College of Medicine , Nishinomiya , Hyogo , Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yoneoka
authors.affiliation: a Department of Biochemistry, Hyogo College of Medicine , Nishinomiya , Hyogo , Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Yoshihara
authors.affiliation: a Department of Biochemistry, Hyogo College of Medicine , Nishinomiya , Hyogo , Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: a Department of Biochemistry, Hyogo College of Medicine , Nishinomiya , Hyogo , Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D004195:Disease Models, Animal; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000378:metabolism; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism
chemical_list: D003300:Copper; D003094:Collagen; D013482:Superoxide Dismutase; D015032:Zinc
keywords: AGE; MMP; SOD1; TIMP; liver fibrosis