PMID- 36423379
OWN - NLM
STAT- MEDLINE
DCOM- 20221206
LR  - 20221221
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 637
DP  - 2022 Dec 31
TI  - Mesenchymal stem cells-derived exosomal miR-24-3p ameliorates non-alcohol fatty 
      liver disease by targeting Keap-1.
PG  - 331-340
LID - S0006-291X(22)01546-7 [pii]
LID - 10.1016/j.bbrc.2022.11.012 [doi]
AB  - The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing 
      worldwide with ill-defined etiology and pathogenesis, and no approved effective 
      therapy is presently available. Exosome-dependent intercellular communication has 
      been identified as a potential signaling involved in tissue repair. 
      Unfortunately, the exact influence and underlying mechanism of mesenchymal stem 
      cells (MSCs)-derived exosome (Exo) in modulating fatty liver have not been well 
      determined. Here in our study, in vitro results initially showed that human 
      umbilical cord-derived mesenchymal stem cells (hUC-MSCs)-derived Exo treatment 
      significantly suppressed lipid accumulation, reactive oxygen species (ROS) 
      generation and inflammatory response in palmitate (PA)-stimulated mouse 
      hepatocytes. Consistently, MSCs-derived Exo administration strongly ameliorated 
      metabolic disorders, hepatic dysfunction and steatosis in high fat diet 
      (HFD)-induced mouse model with NAFLD. Furthermore, Exo derived from MSCs 
      significantly alleviated hepatic lipid metabolism disturbance, inflammation and 
      oxidative stress induced by HFD. Exo treatment resulted in a stronger increase in 
      miR-24-3p expression in hepatocytes. Reducing miR-24-3p in MSCs markedly 
      abrogated the protective effects of Exo in hepatocytes under PA stimulation. 
      Mechanistically, miR-24-3p directly targeted Kelch-like ECH-associated protein 1 
      (Keap-1), and suppressed its expression. In addition, the effects of MSCs-derived 
      exosomal miR-24-3p to restrain lipid accumulation, ROS generation and 
      inflammation in vitro were largely Keap-1 dependent via Keap-1 depression. 
      Collectively, our study demonstrated that MSCs-derived exosomal miR-24-3p had 
      hepaprotective effects through targeting Keap-1 signaling, providing a potential 
      therapeutic value for NAFLD treatment.
CI  - Copyright (c) 2022. Published by Elsevier Inc.
FAU - Du, Xiaolin
AU  - Du X
AD  - Department of Medical Center, The Second Affiliated Hospital of Shandong 
      University of Traditional Chinese Medicine, Jinan, 250001, China. Electronic 
      address: dxl0252@126.com.
FAU - Li, Haiyan
AU  - Li H
AD  - Department of Scientific Research Center, The Second Affiliated Hospital of 
      Shandong University of Traditional Chinese Medicine, Jinan, 250001, China.
FAU - Han, Xingjun
AU  - Han X
AD  - Prevention and Treatment Center, The Second Affiliated Hospital of Shandong 
      University of Traditional Chinese Medicine, Jinan, 250001, China.
FAU - Ma, Wenlu
AU  - Ma W
AD  - Department of Medical Center, The Second Affiliated Hospital of Shandong 
      University of Traditional Chinese Medicine, Jinan, 250001, China. Electronic 
      address: 826036122@qq.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221111
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN24 microRNA, human)
RN  - 0 (Palmitates)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (KEAP1 protein, human)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Inflammation
MH  - Kelch-Like ECH-Associated Protein 1/genetics
MH  - *Mesenchymal Stem Cells
MH  - *MicroRNAs/genetics
MH  - *Non-alcoholic Fatty Liver Disease/genetics/therapy
MH  - Palmitates
MH  - Reactive Oxygen Species
OTO - NOTNLM
OT  - Exosome
OT  - Keap-1
OT  - MSCs
OT  - NAFLD
OT  - miR-24-3p
COIS- Declaration of competing interest The authors see no conflict of interest.
EDAT- 2022/11/25 06:00
MHDA- 2022/12/06 06:00
CRDT- 2022/11/24 18:14
PHST- 2022/10/24 00:00 [received]
PHST- 2022/11/03 00:00 [revised]
PHST- 2022/11/06 00:00 [accepted]
PHST- 2022/11/25 06:00 [pubmed]
PHST- 2022/12/06 06:00 [medline]
PHST- 2022/11/24 18:14 [entrez]
AID - S0006-291X(22)01546-7 [pii]
AID - 10.1016/j.bbrc.2022.11.012 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2022 Dec 31;637:331-340. doi: 
      10.1016/j.bbrc.2022.11.012. Epub 2022 Nov 11.