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Title: Long non-coding RNA APTR promotes the activation of hepatic stellate cells and the progression of liver fibrosis

In this study, we aimed at assessing a role of Alu-mediated p21 transcriptional regulator (APTR) in hepatofibrogenesis. APTR was upregulated in fibrotic liver samples and activated hepatic stellate cells (HSCs). Knockdown of APTR inhibited the activation of HSCs in vitro and mitigated the accumulation of collagen in vivo. Importantly, APTR silencing could abrogate TGF-β{sub 1}-induced upregulation of α-SMA in HSCs. In addition, inhibition of cell cycle and cell proliferation by APTR knockdown was attenuated by p21 siRNA1 in primary HSCs. Finally, serum APTR levels were increased in patients with liver cirrhosis, indicating a potential biomarker for liver cirrhosis. Collectively, evidence is proposed for a new biological role of APTR in hepatofibrogenesis. - Highlights: • APTR is upregulated in fibrotic liver tissues and activated HSCs. • APTR silencing inhibits HSC activation and the progression of liver fibrosis. • Antifibrotic effect of APTR silencing is achieved by increasing p21.
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [5] ; ;  [6] ;  [1]
  1. Department of Gastroenterology, Jinshan Hospital of Fudan University, Jinshan, Shanghai, 201508 (China)
  2. Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 (China)
  3. Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 (China)
  4. Department of Hepatology, Ningbo Yinzhou Second Hospital, Ningbo, 315000 (China)
  5. Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 (China)
  6. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072 (China)
Publication Date:
OSTI Identifier:
22462143
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 463; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; BILIARY TRACT; BIOLOGICAL MARKERS; CARBON TETRACHLORIDE; CELL CYCLE; CELL PROLIFERATION; COLLAGEN; DEOXYURIDINE; FIBROSIS; INHIBITION; LIVER; LIVER CIRRHOSIS; MONOCLINIC LATTICES; PATIENTS; POLYMERASE CHAIN REACTION; RNA