title: lincRNA-p21 inhibits hepatic stellate cell activation and liver fibrogenesis via p21.
abstract: Long non-coding RNAs are involved in various biological processes and diseases. The biological role of long intergenic non-coding RNA-p21 (lincRNA-p21) in liver fibrosis remains unknown before this study. In this study, we observed marked reduction of lincRNA-p21 expression in mice liver fibrosis models and human cirrhotic liver. Over-expression of lincRNA-p21 suppressed activation of hepatic stellate cells (HSCs) in vitro. Lentivirus-mediated lincRNA-p21 transfer into mice decreased the severity of liver fibrosis in vivo. Additionally, lincRNA-p21 reversed the activation of HSCs to their quiescent phenotype. The mRNA levels of lincRNA-p21 and p21 were positively correlated. Our results show that over-expression of lincRNA-p21 promotes up-regulation of p21 at both the mRNA and protein levels. Furthermore, lincRNA-p21 inhibited cell-cycle progression and proliferation of primary HSCs through enhancement of p21 expression. Compared with healthy subjects, serum lincRNA-p21 levels were significantly lower in patients with liver cirrhosis, especially those with decompensation. These findings collectively indicate that lincRNA-p21 is a mediator of HSC activation, supporting its utility as a novel therapeutic target for liver fibrosis.
authors.affiliation: Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Shaolong
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Hepatology, Ningbo Yinzhou Second Hospital, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D015316:Genetic Therapy; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016283:Proto-Oncogene Proteins p21(ras) / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C039919:RNA, recombinant; D012313:RNA; D016283:Proto-Oncogene Proteins p21(ras); D006909:Hydroxyproline
keywords: hepatic stellate cells; liver fibrosis; long intergenic non-coding RNA-p21; long non-coding RNA; p21