title: Up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.
abstract: Although the healthy liver is known to have high regenerative potential, poor liver regeneration under pathological conditions remains a substantial problem. We investigated the key molecules that impair the regeneration of cholestatic liver. C57BL/6 mice were randomly subjected to partial hepatectomy and bile duct ligation (PH+BDL group, n = 16), partial hepatectomy only (PH group, n = 16), or sham operation (Sham group, n = 16). The liver sizes and histological findings were similar in the PH and sham groups 14 days after operation. However, compared with those in the sham group, the livers in mice in the PH+BDL group had a smaller size, a lower cell proliferative activity, and more fibrotic tissue 14 days after the operation, suggesting the insufficient regeneration of the cholestatic liver. Pathway-focused array analysis showed that many genes were up- or down-regulated over 1.5-fold in both PH+BDL and PH groups at 1, 3, 7, and 14 days after treatment. Interestingly, more genes that were functionally related to the extracellular matrix and inflammatory chemokines were found in the PH+BDL group than in the PH group at 7 and 14 days after treatment. Our data suggest that up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.|Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou 510180, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Soyama
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hidaka
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Natsuda
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Tota
authors.initials: T
authors.lastname: Kugiyama
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Zhassulan
authors.initials: Z
authors.lastname: Baimakhanov
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kuroki
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou 510180, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Eguchi
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000293:injuries; D002779:Cholestasis; D002780:Cholestasis, Intrahepatic / Q000209:etiology / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006498:Hepatectomy; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D016326:Extracellular Matrix Proteins