title: Aminoacyl-tRNA synthetase interacting multi-functional protein 1 attenuates liver fibrosis by inhibiting TGFβ signaling.
abstract: The aminoacyl-tRNA synthetase interacting multi-functional protein 1 (AIMP1) participates in a variety of cellular processes, including translation, cell proliferation, inflammation and wound healing. Previously, we showed that the N-terminal peptide of AIMP1 (6-46 aa) induced ERK phosphorylation. Liver fibrosis is characterized by excessive deposition of extracellular matrix, which is induced by TGFβ signaling, and activated ERK is known to induce the phosphorylation of SMAD, thereby inhibiting TGFβ signaling. We assessed whether the AIMP1 peptide can inhibit collagen synthesis in hepatic stellate cells (HSCs) by activating ERK. The AIMP1 peptide induced phosphorylation of SMAD2 via ERK activation, and inhibited the nuclear translocation of SMAD, resulting in a reduction of the synthesis of type I collagen. The AIMP1 peptide attenuated liver fibrosis induced by CCl4, in a dose-dependent manner. Masson-Trichrome staining showed that the AIMP1 peptide reduced collagen deposition. Immunohistochemical staining showed that the levels of α-SMA, TGFβ and type I collagen were all reduced by the AIMP1 peptide. Liver toxicity analysis showed that the AIMP1 peptide improved the levels of relevant biological parameters in the blood. These results suggest that AIMP1 peptide may have potential for development as a therapeutic agent to treat liver fibrosis.
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Gyunggido, Republic of Korea.
authors.forename: Jongchan
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Mi Kwon
authors.initials: MK
authors.lastname: Son
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Pathology, Bundang CHA General Hospital, CHA University, Gyunggido, Republic of Korea.
authors.forename: Kwangil
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Gyunggido, Republic of Korea.
authors.forename: Gi Jin
authors.initials: GJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Gyunggido, Republic of Korea.
authors.forename: Soo-Hong
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Soon-Sun
authors.initials: SS
authors.lastname: Hong
authors.affiliation: Department of Pharmacy, College of Pharmacy, Ajou University, Suwon, Gyunggido, Republic of Korea.
authors.forename: Sang Gyu
authors.initials: SG
authors.lastname: Park
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C077219:small inducible cytokine subfamily E, member 1; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D000604:Amino Acyl-tRNA Synthetases