PMID- 37303049
OWN - NLM
STAT- MEDLINE
DCOM- 20230613
LR  - 20230614
IS  - 1477-3155 (Electronic)
IS  - 1477-3155 (Linking)
VI  - 21
IP  - 1
DP  - 2023 Jun 12
TI  - Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p 
      attenuates inflammatory bowel disease by inhibiting ferroptosis.
PG  - 188
LID - 10.1186/s12951-023-01951-x [doi]
LID - 188
AB  - BACKGROUND: Ferroptosis, a unique form of non-apoptotic cell death, is dependent 
      on iron and lipoperoxidation, and has been shown to be associated with the 
      pathogenesis of inflammatory bowel disease (IBD). Human umbilical cord 
      mesenchymal stem cell-derived exosomes (hucMSC-Ex) are involved in cell survival, 
      immune conditioning, and damage repair. However, the relationship between 
      hucMSC-Ex, IBD, and ferroptosis is unknown. This paper explores the role of 
      hucMSC-Ex in the repair of IBD through the regulation of the ferroptosis 
      signaling pathway. RESULTS: In this study, we used small RNA sequencing to find 
      that miR-129-5p was highly expressed in hucMSC-Ex, and by predicting its 
      targeting to ACSL4, we verified the effect of miR-129-5p on mice IBD in vitro and 
      human colonic epithelial cells (HCoEpiC) in vivo. We found that miR-129-5p 
      reduces ferroptosis in intestinal epithelial cells by targeting ACSL4 to repair 
      IBD, which provides new strategies for the prevention and treatment of IBD. 
      CONCLUSION: In conclusion, our results demonstrate that hucMSC-Ex relieves IBD by 
      targeting ACSL4 with miR-129-5p to inhibit lipid peroxidation (LPO) and 
      ferroptosis, reducing intestinal inflammation and repairing damages. Mechanism of 
      hucMSC-Ex inhibiting ferroptosis in intestinal epithelial cells. System Xc(-) 
      mediates the transport of extracellular cystine into the cell, which gets reduced 
      to cysteine to participate in GSH-mediated metabolism. GPX4 strongly inhibits 
      ferroptosis by helping scavenge reactive oxygen species. The depletion of GSH 
      correlates with decreased GPX4, and the imbalance of the antioxidant system leads 
      to the formation of toxic phospholipid hydroperoxide, which promotes the 
      occurrence of ferroptosis with the participation of irons. HucMSC-Ex has the 
      ability to relieve GSH and GPX4 depletion and repair the intracellular 
      antioxidant system. Ferric ions enter the cytosol through DMT1 and participate in 
      lipid peroxidation. HucMSC-Ex can reduce the expression of DMT1 and alleviate 
      this process. HucMSC-Ex-derived miR-129-5p targets ACSL4 and reduces the 
      expression of ACSL4, an enzyme that mediates the conversion of PUFAs into 
      phospholipids in intestinal epithelial cells, and is a positive regulator of 
      lipid peroxidation. ABBREVIATIONS: GSH, glutathione; GPX4, glutathione peroxidase 
      4; GSSG, oxidized glutathione; DMT1, divalent metal transporter 1; ACSL4, 
      acyl-CoA synthetase long-chain family member 4; PUFAs, polyunsaturated fatty 
      acids; ALOXs, lipoxygenases; CoA, coenzyme A; PL, phospholipid; PLOOH, 
      hydroperoxides, LOH, phospholipid alcohols; LPO, lipid peroxidation.
CI  - (c) 2023. The Author(s).
FAU - Wei, Zhiping
AU  - Wei Z
AD  - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, 
      School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 
      212013, P.R. China.
FAU - Hang, Sanhua
AU  - Hang S
AD  - The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong 
      University, Zhenjiang, Jiangsu, 212300, P.R. China.
FAU - Wiredu Ocansey, Dickson Kofi
AU  - Wiredu Ocansey DK
AD  - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, 
      School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 
      212013, P.R. China.
FAU - Zhang, Zhaoyang
AU  - Zhang Z
AD  - Clinical Lab, Taicang Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, 
      215400, P.R. China.
FAU - Wang, Bo
AU  - Wang B
AD  - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, 
      School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 
      212013, P.R. China.
FAU - Zhang, Xu
AU  - Zhang X
AD  - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, 
      School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 
      212013, P.R. China.
FAU - Mao, Fei
AU  - Mao F
AD  - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, 
      School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 
      212013, P.R. China. maofei2003@ujs.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230612
PL  - England
TA  - J Nanobiotechnology
JT  - Journal of nanobiotechnology
JID - 101152208
RN  - 0 (Antioxidants)
RN  - GAN16C9B8O (Glutathione)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn129 microRNA, human)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Antioxidants
MH  - *Exosomes
MH  - *Ferroptosis
MH  - *Inflammatory Bowel Diseases/therapy
MH  - *Mesenchymal Stem Cells
MH  - Glutathione
MH  - *MicroRNAs/genetics
PMC - PMC10259042
OTO - NOTNLM
OT  - ACSL4
OT  - Ferroptosis
OT  - Inflammatory bowel disease
OT  - Lipid peroxidation
OT  - Mesenchymal stem cell-derived exosomes
OT  - miR-129-5p
COIS- The authors declare no competing interests.
EDAT- 2023/06/12 00:42
MHDA- 2023/06/13 06:42
PMCR- 2023/06/12
CRDT- 2023/06/11 23:13
PHST- 2023/01/13 00:00 [received]
PHST- 2023/06/02 00:00 [accepted]
PHST- 2023/06/13 06:42 [medline]
PHST- 2023/06/12 00:42 [pubmed]
PHST- 2023/06/11 23:13 [entrez]
PHST- 2023/06/12 00:00 [pmc-release]
AID - 10.1186/s12951-023-01951-x [pii]
AID - 1951 [pii]
AID - 10.1186/s12951-023-01951-x [doi]
PST - epublish
SO  - J Nanobiotechnology. 2023 Jun 12;21(1):188. doi: 10.1186/s12951-023-01951-x.