title: Deletion of clock gene Per2 exacerbates cholestatic liver injury and fibrosis in mice.
abstract: The Period 2 (Per2) gene is an important component of the circadian system and is thought to modulate many physiological and pathological processes in mammals. In the previous study, we have disclosed the protective role of Per2 against carbon tetrachloride induced liver injury and fibrosis. Here we further assess the effect of Per2 deficiency on cholestatic hepatic injury and fibrosis. Cholestasis was induced by bile duct ligation (BDL) for 10 days in wild-type (WT) and Per2(-/-) mice. Masson trichrome staining and analysis of α-SMA immunohistochemistry were performed to show the collagen accumulation and the HSC activation, respectively. The mRNA levels of fibrosis-related genes were monitored by quantitative real-time PCR. Following BDL, livers from Per2(-/-) mice exhibited markedly increased extent of bile infarct and extracellular matrix (ECM) deposition compared with WT mice. Furthermore, the expressions of fibrosis-related genes like TNF-α, TGF-β1, Col1α1 and TIMP-1 were dramatically elevated in Per2(-/-) cholestatic liver. Our observations indicated that clock gene Per2 plays a protective role in mediating liver injury and fibrosis during cholestasis.
authors.affiliation: Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing 210094, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Xiamusiya
authors.initials: X
authors.lastname: Kakan
authors.forename: Shiming
authors.initials: S
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.forename: Aiqun
authors.initials: A
authors.lastname: Jia
authors.forename: Chun
authors.initials: C
authors.lastname: Cai
authors.forename: Jianfa
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002779:Cholestasis / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000293:injuries / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C513312:Per2 protein, mouse; D056950:Period Circadian Proteins