title: p16 deficiency promotes nonalcoholic steatohepatitis via regulation of hepatic oxidative stress.
abstract: Nonalcoholic steatohepatitis (NASH) is characterized by excess accumulation of lipids in liver, accompanied with hepatocyte injury, cell death and inflammation. Although p16 is known as tumor suppressor in multiple cancer types, it remains unclear whether p16 plays a critical role in NASH. To determine whether p16 could play a role in the pathogenesis of NASH, wild-type mice and p16-/-mice were fed on a methionine and choline-deficient (MCD) diet for 3 weeks, and liver steatosis, fibrosis, and inflammation were evaluated. Our data show that p16-/-mice fed with MCD diet displayed more significant hepatic steatosis, hepatocyte damage, increased oxidative stress and inflammatory cell infiltration compared to MCD-fed WT mice. It was also clear that the increased ROS and the accumulation of lipid in BEL-7402 cells occurred when p16 expression was depleted with siRNA. These findings indicate that p16 may play a critical role in the development of NASH by reining in ROS production and by inhabiting inflammatory response.
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Fangqiao
authors.initials: F
authors.lastname: Lv
authors.affiliation: The State Key Laboratory of Reproductive Medicine, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: The State Key Laboratory of Reproductive Medicine, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: An
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing, China. Electronic address: yutongw@ccmu.edu.cn.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002796:Choline Deficiency / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency / Q000235:genetics*; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005526:Food, Formulated / Q000009:adverse effects; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008715:Methionine / Q000172:deficiency; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: C000614131:CDKN2A protein, human; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D034741:RNA, Small Interfering; D008715:Methionine
keywords: NASH; Oxidative stress; p16