Exosomes Derived from BMSCs Ameliorate Intestinal Ischemia-Reperfusion Injury by Regulating miR-144-3p-Mediated Oxidative Stress.
BMSCs
Exosomes
Intestinal ischemia–reperfusion injury
Oxidative stress
PTEN/Akt/Nrf2
miR-144-3p
Journal
Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
05
12
2021
accepted:
10
02
2022
pubmed:
28
5
2022
medline:
26
10
2022
entrez:
27
5
2022
Statut:
ppublish
Résumé
Intestinal ischemia-reperfusion (I/R) injury is a critical pathophysiological process involved in many acute and critical diseases, and it may seriously threaten the lives of patients. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) may be an effective therapeutic approach for I/R injury. This study aimed to investigate the role and possible mechanism of BMSC-exos in intestinal I/R injury in vivo and in vitro based on the miR-144-3p and PTEN/Akt/Nrf2 pathways. BMSC-exos were isolated from mouse BMSCs by super centrifugation methods. The effects of BMSC-exos on I/R intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway were explored in vivo and in vitro. Furthermore, the relationship between miR-144-3p and PTEN was confirmed by a dual-luciferase reporter assay. The miR-144-3p mimic and inhibitor were used to further clarify the role of miR-144-3p in the mitigation of intestinal I/R by BMSC-exos. BMSC-exos effectively alleviated intestinal pathological injury, reduced intestinal cell apoptosis, relieved oxidative stress and regulated the PTEN/Akt/Nrf2 pathway in vivo and in vitro. In addition, miR-144-3p was significantly reduced in the oxygen and glucose deprivation/reperfusion cell model, and miR-144-3p could directly target PTEN to regulate its expression. Additional studies showed that changing the expression of miR-144-3p in BMSC-exos significantly affected the regulation of intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway in I/R, suggesting that miR-144-3p in BMSC-exos plays an important role in regulating the PTEN/Akt/Nrf2 during intestinal I/R. BMSC-exos carrying miR-144-3p alleviated intestinal I/R injury by regulating oxidative stress.
Sections du résumé
BACKGROUND
Intestinal ischemia-reperfusion (I/R) injury is a critical pathophysiological process involved in many acute and critical diseases, and it may seriously threaten the lives of patients. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) may be an effective therapeutic approach for I/R injury.
AIMS
This study aimed to investigate the role and possible mechanism of BMSC-exos in intestinal I/R injury in vivo and in vitro based on the miR-144-3p and PTEN/Akt/Nrf2 pathways.
METHODS
BMSC-exos were isolated from mouse BMSCs by super centrifugation methods. The effects of BMSC-exos on I/R intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway were explored in vivo and in vitro. Furthermore, the relationship between miR-144-3p and PTEN was confirmed by a dual-luciferase reporter assay. The miR-144-3p mimic and inhibitor were used to further clarify the role of miR-144-3p in the mitigation of intestinal I/R by BMSC-exos.
RESULTS
BMSC-exos effectively alleviated intestinal pathological injury, reduced intestinal cell apoptosis, relieved oxidative stress and regulated the PTEN/Akt/Nrf2 pathway in vivo and in vitro. In addition, miR-144-3p was significantly reduced in the oxygen and glucose deprivation/reperfusion cell model, and miR-144-3p could directly target PTEN to regulate its expression. Additional studies showed that changing the expression of miR-144-3p in BMSC-exos significantly affected the regulation of intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway in I/R, suggesting that miR-144-3p in BMSC-exos plays an important role in regulating the PTEN/Akt/Nrf2 during intestinal I/R.
CONCLUSIONS
BMSC-exos carrying miR-144-3p alleviated intestinal I/R injury by regulating oxidative stress.
Identifiants
pubmed: 35624329
doi: 10.1007/s10620-022-07546-0
pii: 10.1007/s10620-022-07546-0
doi:
Substances chimiques
Glucose
IY9XDZ35W2
MicroRNAs
0
NF-E2-Related Factor 2
0
Oxygen
S88TT14065
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
MIRN144 microRNA, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5090-5106Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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