PMID- 33895973 OWN - NLM STAT- MEDLINE DCOM- 20210929 LR - 20211204 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 48 IP - 4 DP - 2021 Apr TI - Modulation of autophagy as the target of mesenchymal stem cells-derived conditioned medium in rat model of myocardial ischemia/reperfusion injury. PG - 3337-3348 LID - 10.1007/s11033-021-06359-0 [doi] AB - 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 mul) 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. FAU - Mokhtari, Behnaz AU - Mokhtari B AUID- ORCID: 0000-0002-3355-9869 AD - Physiology Research Center, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran. AD - Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran. FAU - Badalzadeh, Reza AU - Badalzadeh R AUID- ORCID: 0000-0002-8092-7820 AD - Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran. AD - Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran. FAU - Aboutaleb, Nahid AU - Aboutaleb N AUID- ORCID: 0000-0002-7514-5939 AD - Physiology Research Center, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran. Aboutaleb.n@iums.ac.ir. AD - Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran. Aboutaleb.n@iums.ac.ir. LA - eng GR - 97-2-3-33054/Iran University of Medical Sciences/ PT - Journal Article DEP - 20210425 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (Culture Media, Conditioned) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.1 (ULK1 protein, rat) SB - IM MH - Animals MH - *Autophagy MH - Autophagy-Related Protein-1 Homolog MH - Culture Media, Conditioned/*pharmacology MH - Disease Models, Animal MH - Fibrosis MH - Heart/*drug effects/physiopathology MH - Humans MH - Male MH - *Mesenchymal Stem Cells MH - Myocardial Reperfusion Injury/*drug therapy/physiopathology MH - Rats MH - Rats, Wistar MH - TOR Serine-Threonine Kinases OTO - NOTNLM OT - Autophagy OT - Conditioned medium OT - Ischemia/reperfusion injury OT - Mesenchymal stem cells EDAT- 2021/04/26 06:00 MHDA- 2021/09/30 06:00 CRDT- 2021/04/25 20:56 PHST- 2021/02/09 00:00 [received] PHST- 2021/04/16 00:00 [accepted] PHST- 2021/04/26 06:00 [pubmed] PHST- 2021/09/30 06:00 [medline] PHST- 2021/04/25 20:56 [entrez] AID - 10.1007/s11033-021-06359-0 [pii] AID - 10.1007/s11033-021-06359-0 [doi] PST - ppublish SO - Mol Biol Rep. 2021 Apr;48(4):3337-3348. doi: 10.1007/s11033-021-06359-0. Epub 2021 Apr 25.