PMID- 32201276
OWN - NLM
STAT- MEDLINE
DCOM- 20200615
LR  - 20200615
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 253
DP  - 2020 Jul 15
TI  - Peroxisome proliferator-activated receptor gamma inhibits hepatic stellate cell 
      activation regulated by miR-942 in chronic hepatitis B liver fibrosis.
PG  - 117572
LID - S0024-3205(20)30320-9 [pii]
LID - 10.1016/j.lfs.2020.117572 [doi]
AB  - AIMS: Liver fibrosis is a chronic liver disease characterized by hepatic stellate 
      cell (HSC) activation. Peroxisome proliferator-activated receptor gamma (PPARgamma) 
      play an important role in HSC activation. This study aimed to investigate the 
      role of PPARgamma in the progression of human hepatic fibrosis and the mechanism by 
      which microRNA-942 regulates HSC activation. METHODS: 70 chronic hepatitis B 
      (CHB) patients liver tissues were used to assess PPARgamma, alpha-SMA and miR-942 levels 
      by immunoblot and real-time PCR. Human primary HSCs or LX2 cells were used to 
      perform multiple molecular experiments based on the transfection of small 
      interfering RNA (siRNA) or co-transfection of microRNA inhibitor. Site-directed 
      mutagenesis and luciferase reporter assays were used to identify miR-942 targets. 
      miR-942 expression and localization in hepatic fibrosis and co-localization 
      between alpha-SMA were determined by fluorescence in situ hybridization (FISH). KEY 
      FINDINGS: The mRNA expression of PPARgamma was decreased in activated HSCs and CHB 
      patients with liver fibrosis, which was negatively correlated with F stage and 
      alpha-SMA. miR-942 negatively regulates PPARgamma expression via targeting the PPARgamma 
      3'UTR. Inhibiting PPARgamma promoted TGFbeta1 induced HSC activation, and this effect 
      was blocked after inhibiting the miR-942. Moreover, miR-942 was mainly expressed 
      in fibrous septa and negatively correlated with PPARgamma in liver fibrosis. 
      SIGNIFICANCE: PPARgamma targeting by miR-942 and decreasing HSC activation in human 
      hepatic fibrosis. Hence, regulating PPARgamma may be a promising therapeutic strategy 
      for hepatic fibrosis.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Tao, Le
AU  - Tao L
AD  - Laboratory of Liver Disease, Department of Infectious Disease, Putuo Hospital, 
      Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
FAU - Wu, Liu
AU  - Wu L
AD  - Laboratory of Liver Disease, Department of Infectious Disease, Putuo Hospital, 
      Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese 
      Medicine, Shanghai 200062, China.
FAU - Ma, Wen-Ting
AU  - Ma WT
AD  - Laboratory of Liver Disease, Department of Infectious Disease, Putuo Hospital, 
      Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
FAU - Yang, Guang-Yue
AU  - Yang GY
AD  - Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese 
      Medicine, Shanghai 200062, China.
FAU - Zhang, Jie
AU  - Zhang J
AD  - Laboratory of Liver Disease, Department of Infectious Disease, Putuo Hospital, 
      Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
FAU - Xue, Dong-Ying
AU  - Xue DY
AD  - Laboratory of Liver Disease, Department of Infectious Disease, Putuo Hospital, 
      Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
FAU - Chen, Bei
AU  - Chen B
AD  - Laboratory of Liver Disease, Department of Infectious Disease, Putuo Hospital, 
      Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. 
      Electronic address: bei_c@sina.com.
FAU - Liu, Cheng
AU  - Liu C
AD  - Laboratory of Liver Disease, Department of Infectious Disease, Putuo Hospital, 
      Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; 
      Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese 
      Medicine, Shanghai 200062, China; Shanghai Putuo Central School of Clinical 
      Medicine, Anhui Medical University, Shanghai, China. Electronic address: 
      liucheng0082010@163.com.
LA  - eng
PT  - Journal Article
DEP - 20200319
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (ACTA2 protein, human)
RN  - 0 (Actins)
RN  - 0 (MIRN942 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (PPAR gamma)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
MH  - Actins
MH  - Base Sequence
MH  - Gene Expression Regulation
MH  - Hepatic Stellate Cells/metabolism
MH  - *Hepatitis B, Chronic/metabolism/therapy
MH  - Humans
MH  - *Liver Cirrhosis/metabolism/therapy
MH  - MicroRNAs/metabolism
MH  - Optical Imaging/methods
MH  - PPAR gamma/*metabolism
MH  - Transforming Growth Factor beta1/*metabolism
OTO - NOTNLM
OT  - Liver fibrosis
OT  - PPAR gamma, hepatic stellate cell
OT  - microRNA-942
COIS- Declaration of competing interest None declared.
EDAT- 2020/03/24 06:00
MHDA- 2020/06/17 06:00
CRDT- 2020/03/24 06:00
PHST- 2019/10/27 00:00 [received]
PHST- 2020/03/10 00:00 [revised]
PHST- 2020/03/17 00:00 [accepted]
PHST- 2020/03/24 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2020/03/24 06:00 [entrez]
AID - S0024-3205(20)30320-9 [pii]
AID - 10.1016/j.lfs.2020.117572 [doi]
PST - ppublish
SO  - Life Sci. 2020 Jul 15;253:117572. doi: 10.1016/j.lfs.2020.117572. Epub 2020 Mar 
      19.