PMID- 37328872
OWN - NLM
STAT- MEDLINE
DCOM- 20230623
LR  - 20230623
IS  - 1477-3155 (Electronic)
IS  - 1477-3155 (Linking)
VI  - 21
IP  - 1
DP  - 2023 Jun 16
TI  - Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via 
      downregulating YAP/LOXL2 pathway.
PG  - 195
LID - 10.1186/s12951-023-01942-y [doi]
LID - 195
AB  - Lysyl oxidase-like 2 (LOXL2) is an extracellular copper-dependent enzyme that 
      plays a central role in fibrosis by catalyzing the crosslinking and deposition of 
      collagen. Therapeutic LOXL2 inhibition has been shown to suppress liver fibrosis 
      progression and promote its reversal. This study investigates the efficacy and 
      underlying mechanisms of human umbilical cord-derived exosomes (MSC-ex) in LOXL2 
      inhibition of liver fibrosis. MSC-ex, nonselective LOX inhibitor 
      beta-aminopropionitrile (BAPN), or PBS were administered into carbon tetrachloride 
      (CCl4)-induced fibrotic livers. Serum LOXL2 and collagen crosslinking were 
      assessed histologically and biochemically. MSC-ex's mechanisms on LOXL2 
      regulation were investigated in human hepatic stellate cell line LX-2. We found 
      that systemic administration of MSC-ex significantly reduced LOXL2 expression and 
      collagen crosslinking, delaying the progression of CCl4-induced liver fibrosis. 
      Mechanically, RNA-sequencing and fluorescence in situ hybridization (FISH) 
      indicated that miR-27b-3p was enriched in MSC-ex and exosomal miR-27b-3p 
      repressed Yes-associated protein (YAP) expression by targeting its 3' 
      untranslated region in LX-2. LOXL2 was identified as a novel downstream target 
      gene of YAP, and YAP bound to the LOXL2 promoter to positively regulate 
      transcription. Additionally, the miR-27b-3p inhibitor abrogated the anti-LOXL2 
      abilities of MSC-ex and diminished the antifibrotic efficacy. miR-27b-3p 
      overexpression promoted MSC-ex mediated YAP/LOXL2 inhibition. Thus, MSC-ex may 
      suppress LOXL2 expression through exosomal miR-27b-3p mediated YAP 
      down-regulation. The findings here may improve our understanding of MSC-ex in 
      liver fibrosis alleviation and provide new opportunities for clinical treatment.
CI  - (c) 2023. The Author(s).
FAU - Cheng, Fang
AU  - Cheng F
AD  - Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu 
      University, Jiangsu University, Changzhou, 213017, China.
AD  - Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, 
      Jiangsu University, Zhenjiang, 212001, China.
FAU - Yang, Fuji
AU  - Yang F
AD  - Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu 
      University, Jiangsu University, Changzhou, 213017, China.
AD  - Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, 
      Jiangsu University, Zhenjiang, 212001, China.
FAU - Wang, Yanjin
AU  - Wang Y
AD  - Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu 
      University, Jiangsu University, Changzhou, 213017, China.
AD  - Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, 
      Jiangsu University, Zhenjiang, 212001, China.
FAU - Zhou, Jing
AU  - Zhou J
AD  - Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine, 
      Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213017, China.
AD  - Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu 
      University (Wujin Clinical College of Xuzhou Medical University), Changzhou, 
      213017, China.
FAU - Qian, Hui
AU  - Qian H
AD  - Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, 
      Jiangsu University, Zhenjiang, 212001, China.
AD  - Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine, 
      Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213017, China.
FAU - Yan, Yongmin
AU  - Yan Y
AD  - Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu 
      University, Jiangsu University, Changzhou, 213017, China. yym@wjrmyy.cn.
AD  - Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine, 
      Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213017, China. 
      yym@wjrmyy.cn.
AD  - Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu 
      University (Wujin Clinical College of Xuzhou Medical University), Changzhou, 
      213017, China. yym@wjrmyy.cn.
LA  - eng
GR  - 82272421/Yongmin Yan/
PT  - Journal Article
DEP - 20230616
PL  - England
TA  - J Nanobiotechnology
JT  - Journal of nanobiotechnology
JID - 101152208
RN  - 9007-34-5 (Collagen)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN27 microRNA, human)
SB  - IM
MH  - Humans
MH  - Collagen/metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Liver Cirrhosis/chemically induced/drug therapy/metabolism
MH  - *Mesenchymal Stem Cells/metabolism
MH  - *MicroRNAs/metabolism
PMC - PMC10273609
OTO - NOTNLM
OT  - Collagen crosslinking
OT  - Exosome
OT  - LOXL2
OT  - Liver fibrosis
OT  - MSC
OT  - YAP
OT  - miR-27b-3p
COIS- The authors declared no competing financial interest.
EDAT- 2023/06/17 05:11
MHDA- 2023/06/19 13:09
PMCR- 2023/06/16
CRDT- 2023/06/16 23:41
PHST- 2023/02/28 00:00 [received]
PHST- 2023/05/29 00:00 [accepted]
PHST- 2023/06/19 13:09 [medline]
PHST- 2023/06/17 05:11 [pubmed]
PHST- 2023/06/16 23:41 [entrez]
PHST- 2023/06/16 00:00 [pmc-release]
AID - 10.1186/s12951-023-01942-y [pii]
AID - 1942 [pii]
AID - 10.1186/s12951-023-01942-y [doi]
PST - epublish
SO  - J Nanobiotechnology. 2023 Jun 16;21(1):195. doi: 10.1186/s12951-023-01942-y.