PMID- 37621754
OWN - NLM
STAT- MEDLINE
DCOM- 20230828
LR  - 20230828
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 29
IP  - 29
DP  - 2023 Aug 7
TI  - Antagonizing adipose tissue-derived exosome miR-103-hepatocyte phosphatase and 
      tensin homolog pathway alleviates autophagy in non-alcoholic steatohepatitis: A 
      trans-cellular crosstalk.
PG  - 4528-4541
LID - 10.3748/wjg.v29.i29.4528 [doi]
AB  - BACKGROUND: Obesity plays a vital role in the occurrence and development of 
      non-alcoholic steatohepatitis (NASH). However, the underlining mechanism is still 
      unclear, where adipose tissue (AT) derived exosomes may actively participate. 
      MicroRNAs (miRNAs) are commonly secreted from exosomes for cell communication. 
      Though the regulation of miR-103 on insulin sensitivity has been reported, the 
      specific role of AT-derived exosomes miR-103 in NASH is still vague and further 
      investigation may provide novel therapeutic choices. AIM: To determine the 
      specific role of AT-derived exosomes miR-103 in developing NASH through various 
      methods. METHODS: The expression levels of miR-103 in the AT-derived exosomes and 
      livers were detected and compared between NASH mice and control. The effect of 
      miR-103 on NASH progression was also explored by antagonizing miR-103, including 
      steatosis and inflammation degree changes. The interaction between miR-103 and 
      the autophagy-related gene phosphatase and tensin homolog (PTEN) was confirmed by 
      dual-luciferase reporter assay. The role of the interaction between miR-103 and 
      PTEN on autophagy was verified in NASH-like cells. Finally, the effects of 
      miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through 
      animal experiments. RESULTS: The expression of miR-103 was increased in NASH 
      mice, compared to the control, and inhibition of miR-103 could alleviate NASH. 
      The results of the dual-luciferase reporter assay showed miR-103 could interact 
      with PTEN. MiR-103-anta decreased p-AMPKa, p-mammalian target of rapamycin 
      (mTOR), and p62 but increased the protein levels of PTEN and LC3-II/I and the 
      number of autophagosomes in NASH mice. Similar results were also observed in 
      NASH-like cells, and further experiments showed PTEN silencing inhibited the 
      effect of miR-103-anta. AT derived-exosome miR-103 aggravated NASH and increased 
      the expressions of p-AMPKa, p-mTOR, and p62 but decreased the protein levels of 
      PTEN and LC3-II/I and the number of autophagosomes in mice. CONCLUSION: AT 
      derived-exosome increased the levels of miR-103 in the liver, and miR-103 
      aggravated NASH. Mechanically, miR-103 could interact with PTEN and inhibit 
      autophagy.
CI  - (c)The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Lu, Miao-Miao
AU  - Lu MM
AD  - Endoscopy Center, Children's Hospital of Zhejiang University School of Medicine, 
      Hangzhou 310003, Zhejiang Province, China.
FAU - Ren, Yue
AU  - Ren Y
AD  - Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, 
      Zhejiang Province, China.
FAU - Zhou, Yu-Wei
AU  - Zhou YW
AD  - Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, 
      Zhejiang Province, China.
FAU - Xu, Ling-Ling
AU  - Xu LL
AD  - Department of Gastroenterology, The Second People's Hospital of Yuhang District, 
      Hangzhou 310003, Zhejiang Province, China.
FAU - Zhang, Meng-Meng
AU  - Zhang MM
AD  - Department of Gastroenterology, Hangzhou Shangcheng District People's Hospital, 
      Hangzhou 310003, Zhejiang Province, China.
FAU - Ding, Lin-Ping
AU  - Ding LP
AD  - Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, 
      Zhejiang Province, China.
FAU - Cheng, Wei-Xin
AU  - Cheng WX
AD  - Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, 
      Zhejiang Province, China.
FAU - Jin, Xi
AU  - Jin X
AD  - Department of Gastroenterology, The First Affiliated Hospital of Zhejiang 
      University School of Medicine, Hangzhou 310003, Zhejiang Province, China. 
      jxfl007@zju.edu.cn.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Tensins)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Exosomes/genetics
MH  - Tensins
MH  - *Non-alcoholic Fatty Liver Disease/genetics
MH  - Hepatocytes
MH  - Autophagy
MH  - AMP-Activated Protein Kinases
MH  - Adipose Tissue
MH  - Mammals
PMC - PMC10445005
OTO - NOTNLM
OT  - Exosomes
OT  - Non-alcoholic steatohepatitis
OT  - Nonalcoholic fatty liver disease
OT  - Phosphatase and tensin homolog
COIS- Conflict-of-interest statement: All the authors report no relevant conflicts of 
      interest for this article.
EDAT- 2023/08/25 06:42
MHDA- 2023/08/28 06:42
PMCR- 2023/08/07
CRDT- 2023/08/25 03:52
PHST- 2023/04/05 00:00 [received]
PHST- 2023/06/11 00:00 [revised]
PHST- 2023/07/04 00:00 [accepted]
PHST- 2023/08/28 06:42 [medline]
PHST- 2023/08/25 06:42 [pubmed]
PHST- 2023/08/25 03:52 [entrez]
PHST- 2023/08/07 00:00 [pmc-release]
AID - 10.3748/wjg.v29.i29.4528 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2023 Aug 7;29(29):4528-4541. doi: 
      10.3748/wjg.v29.i29.4528.