title: Adiponectin-derived active peptide ADP355 exerts anti-inflammatory and anti-fibrotic activities in thioacetamide-induced liver injury.
abstract: Adiponectin is an adipocyte-derived circulating protein with beneficial effects on injured livers. Adiponectin-deficient (adipo(-/-)) mice develop enhanced liver fibrosis, suggesting that adiponectin could be a therapeutic target for liver injury. In the present study, we investigated the protective role of ADP355, an adiponectin-based active short peptide, in thioacetamide (TAA)-induced acute injury and chronic liver fibrosis in mice. ADP355 remarkably reduced TAA-induced necroinflammation and liver fibrosis. ADP355 treatment increased liver glycogen, decreased serum alanine transaminase and alkaline phosphatase activity, and promoted body weight gain, hyper-proliferation and hypo-apoptosis. In addition, ADP355 administration suppressed the TAA-induced activation of hepatic stellate cells and macrophages in the liver. These were associated with the inactivation of TGF-β1/SMAD2 signaling and the promotion of AMPK and STAT3 signaling. Sensitivity of adipo(-/-) mice to chronic liver injury was decreased with ADP355. In conclusion, ADP355 could mimic adiponectin's action and may be suitable for the preclinical or clinical therapy of chronic liver injury.
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology; Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China, Tianjin Medical University, Tianjin, China.|School of Life Science, Shanxi Normal University, Linfen, China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Zimu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Huang
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Xixi
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Logistic College of CAPF, Tianjin, China.
authors.forename: Zha
authors.initials: Z
authors.lastname: la Gahu
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology; Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology; Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Da
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Daiqing
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology; Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China, Tianjin Medical University, Tianjin, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: State Key laboratory of Pharmaceutical Biotechnology, and Department of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.|Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology; Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China, Tianjin Medical University, Tianjin, China.|Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Rongxin
authors.initials: R
authors.lastname: Zhang
mesh_terms: D052242:Adiponectin / Q000737:chemistry* / Q000172:deficiency / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008111:Liver Function Tests; D008115:Liver Regeneration; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013853:Thioacetamide / Q000009:adverse effects
chemical_list: D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D009842:Oligopeptides; D050796:STAT3 Transcription Factor; C000603754:asparaginyl-isoleucyl-prolyl-norvalyl-leucyl-tyrosyl-seryl-phenylalanyl-alanyl-serinamide; D013853:Thioacetamide