Modulation of autophagy as the target of mesenchymal stem cells-derived conditioned medium in rat model of myocardial ischemia/reperfusion injury.
Autophagy
Conditioned medium
Ischemia/reperfusion injury
Mesenchymal stem cells
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
09
02
2021
accepted:
16
04
2021
pubmed:
26
4
2021
medline:
30
9
2021
entrez:
25
4
2021
Statut:
ppublish
Résumé
Human amniotic membrane mesenchymal stem cells-derived conditioned medium (hAM-MSCs-CM) has positive effects against myocardial ischemia/reperfusion (MI/R) injury. However, it needs further investigations how hAM-MSCs-CM leads to the cell survival under MI/R via modulation of autophagy. The purpose of this study is investigating the effects of hAM-MSCs-CM in a rat model of MI/R injury by focusing on the role of autophagy as one of its possible mechanisms. Male Wistar rats (44 rats, 175-200 g) were randomly divided into four groups: Sham, MI/R, culture media-receiving and conditioned medium-receiving. MI/R was induced by 30 min of left anterior descending coronary artery ligation. After 15 min reperfusion, culture media or hAM-MSCs-CM (150 μl) were injected intramyocardially. At the end of the experiment, CK-MB, autophagy markers, phosphorylated and total forms of mTOR and ULK1, cardiac function and fibrosis were measured. hAM-MSCs-CM significantly decreased CK-MB levels (P < 0.0001), and also the mRNA levels of Beclin1 (P < 0.0001), LC3 (P = 0.012) and p62 (P = 0.003). In addition, hAM-MSCs-CM significantly reduced Beclin1, LC3II/LC3I and p62 protein levels (P < 0.0001), and increased p-mTOR/mTOR (P = 0.022) and p-ULK1/ULK1 (P < 0.0001) expressions. Moreover, hAM-MSCs-CM improved cardiac function and decreased fibrosis (P < 0.0001). This study showed cardioprotective effects of hAM-MSCs-CM against MI/R injury through modulation of autophagy via mTOR/ULK1 pathway. Based on these findings, it can be concluded that hAM-MSCs-CM can be offered as an attractive candidate for attenuation of MI/R injury in future, but needs further investigations.
Identifiants
pubmed: 33895973
doi: 10.1007/s11033-021-06359-0
pii: 10.1007/s11033-021-06359-0
doi:
Substances chimiques
Culture Media, Conditioned
0
mTOR protein, rat
EC 2.7.1.1
Autophagy-Related Protein-1 Homolog
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
ULK1 protein, rat
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3337-3348Subventions
Organisme : Iran University of Medical Sciences
ID : 97-2-3-33054
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