PMID- 37207965
OWN - NLM
STAT- MEDLINE
DCOM- 20240304
LR  - 20240307
IS  - 0210-5705 (Print)
IS  - 0210-5705 (Linking)
VI  - 47
IP  - 3
DP  - 2024 Mar
TI  - GATA3 promotes the autophagy and activation of hepatic stellate cell in hepatic 
      fibrosis via regulating miR-370/HMGB1 pathway.
PG  - 219-229
LID - S0210-5705(23)00336-9 [pii]
LID - 10.1016/j.gastrohep.2023.05.005 [doi]
AB  - BACKGROUND: Hepatic fibrosis (HF) is a common result of the repair process of 
      various chronic liver diseases. Hepatic stellate cells (HSCs) activation is the 
      central link in the occurrence of HF. METHODS: ELISA and histological analysis 
      were performed to detect the pathological changes of liver tissues. In vitro, 
      HSCs were treated with TGF-beta1 as HF cell model. Combination of GATA-binding 
      protein 3 (GATA3) and miR-370 gene promoter was ensured by ChIP and luciferase 
      reporter assay. Autophagy was monitored by observing the GFP-LC3 puncta 
      formation. The interaction between miR-370 and high mobility group box 1 protein 
      (HMGB1) was verified by luciferase reporter assay. RESULTS: CCl(4)-induced HF 
      mice exhibited an increase of ALT and AST, and severe damage and fibrosis of 
      liver tissues. GATA3 and HMGB1 were up-regulated, and miR-370 was down-regulated 
      in CCl(4)-induced HF mice and activated HSCs. GATA3 enhanced expression of the 
      autophagy-related proteins and activation markers in the activated HSCs. 
      Inhibition of autophagy partly reversed GATA3-induced activation of HSCs and the 
      promotion of GATA3 to hepatic fibrosis. Moreover, GATA3 suppressed miR-370 
      expression via binding with its promotor, and enhanced HMGB1 expression in HSCs. 
      Increasing of miR-370 inhibited HMGB1 expression by directly targeting its mRNA 
      3'-UTR. The promotion of GATA3 to TGF-beta1-induced HSCs autophagy and activation 
      was abrogated by miR-370 up-regulation or HMGB1 knockdown. CONCLUSIONS: This work 
      demonstrates that GATA3 promotes autophagy and activation of HSCs by regulating 
      miR-370/HMGB1 signaling pathway, which contributes to accelerate HF. Thus, this 
      work suggests that GATA3 may be a potential target for prevention and treatment 
      of HF.
CI  - Copyright (c) 2023 Elsevier Espana, S.L.U. All rights reserved.
FAU - Xie, Zhengyuan
AU  - Xie Z
AD  - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang 
      University, Nanchang 330006, China. Electronic address: xzytg2021@163.com.
FAU - Li, Yangyang
AU  - Li Y
AD  - Medical College of Nanchang University, Nanchang 330006, China.
FAU - Xiao, Peiguang
AU  - Xiao P
AD  - Medical College of Nanchang University, Nanchang 330006, China.
FAU - Ke, Shanmiao
AU  - Ke S
AD  - Medical College of Nanchang University, Nanchang 330006, China.
LA  - eng
LA  - spa
PT  - Journal Article
DEP - 20230518
PL  - Spain
TA  - Gastroenterol Hepatol
JT  - Gastroenterologia y hepatologia
JID - 8406671
RN  - 0 (Gata3 protein, mouse)
RN  - 0 (HMGB1 Protein)
RN  - EC 1.13.12.- (Luciferases)
RN  - 0 (MicroRNAs)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (HMGB1 protein, mouse)
RN  - 0 (MIRN370 microRNA, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Autophagy
MH  - Hepatic Stellate Cells
MH  - *HMGB1 Protein
MH  - Liver Cirrhosis
MH  - Luciferases
MH  - *MicroRNAs
MH  - Transforming Growth Factor beta1
OTO - NOTNLM
OT  - Autophagy
OT  - GATA3
OT  - HMGB1
OT  - Hepatic fibrosis
OT  - Hepatic stellate cell
EDAT- 2023/05/20 09:42
MHDA- 2024/03/04 06:49
CRDT- 2023/05/19 19:27
PHST- 2022/12/07 00:00 [received]
PHST- 2023/04/16 00:00 [revised]
PHST- 2023/05/10 00:00 [accepted]
PHST- 2024/03/04 06:49 [medline]
PHST- 2023/05/20 09:42 [pubmed]
PHST- 2023/05/19 19:27 [entrez]
AID - S0210-5705(23)00336-9 [pii]
AID - 10.1016/j.gastrohep.2023.05.005 [doi]
PST - ppublish
SO  - Gastroenterol Hepatol. 2024 Mar;47(3):219-229. doi: 
      10.1016/j.gastrohep.2023.05.005. Epub 2023 May 18.