Exosomes derived from cardiac progenitor cells attenuate CVB3-induced apoptosis via abrogating the proliferation of CVB3 and modulating the mTOR signaling pathways

Abstract

Viral myocarditis is potentially fatal and lacking a specific treatment. Exosomes secreted by cardiac progenitor cells (CPCs) have emerged as a promising tool for cardioprotection and repair. In this study, we investigated whether CPCsderived exosomes (CPCs-Ex) could utilize the mTOR signal pathway to reduce the apoptosis in viral myocarditis. In vitro, exosomes were, respectively, added to H9C2 cells after CVB3 infection to detect the anti-apoptosis effect of CPCs-Ex. Compared with the controls, the apoptosis rate was reduced, accompanied with the depressed expression of viral capsid protein 1 (VP1) and pro-apoptosis factors of Bim/caspase families. Meanwhile, the phosphorylation of Akt, mTOR, and p70S6K were promoted, but that of 4EBP1 was suppressed. In vivo, the results of apoptosis, expression of CVB3 and pro-apoptosis factors, and phosphorylation of Akt/mTOR factors of CVB3-infected cardiomyocytes were consistent with that of vitro. Following that, we use Rapamycin and MK-2206 to inhibit the Akt/mTOR signaling pathway, meanwhile, Rattus 4EBP1, p70S6K, Akt1 and Akt2 were transfected to H9C2 cells to establish the stably transfected cell lines. In the group with Rapamycin or MK-2206 pretreatment, CPCs-Ex also could decrease the apoptosis of H9C2 cells and expression of CVB3 mRNA, followed by decreased expression of apoptosis factors. In Akt2, p70S6K and 4EBP1 overexpression groups, CPCs-Ex promoted CVB3-induced apoptosis, VP1 expression and cleavage of caspase-3. Our results therefore identify CPCs-Ex exerts an anti-apoptosis effect in CVB3-infected cells by abrogating the proliferation of CVB3 and modulating the mTOR signaling pathways as well as the expression of Bcl-2 and caspase families. Viral myocarditis, mainly caused by CVB3 infection, is lacking a specific treatment. Our study identified an antiapoptosis role of CPCs-Ex in CVB3-infected cells and rats, which shown that CPCs-Ex may be an effective tool to treat viral myocarditis. We believe that with more in-depth research on the functionality of CPCs-Ex, there will be a breakthrough in the treatment of viral myocarditis.

RETRACTED ARTICLE: Bone Marrow Mesenchymal Stem Cell-Derived Exosomal MicroRNA-133a Restrains Myocardial Fibrosis and Epithelial–Mesenchymal Transition in Viral Myocarditis Rats Through Suppressing MAML1

“…Additionally, changed exosomal miRNAs are also found to be linked with the pathogenesis of CVB3-induced myocarditis [ 14 ]. Exosomes derived from cardiac progenitor cells ease CVB3-induced apoptosis via restraining the proliferation of CVB3 in VMC [ 24 ]. This study explored the regulatory mechanism of BMSC-derived exosomal miR-133 on myocardial fibrosis and EMT in VMC rats (Additional file 1 : Fig.…”

In vitro and in vivo antiviral activity of a fluoronucleoside analog, NCC, against Coxsackie virus B3

“…in this pathway, cytochrome c is released from the mitochondria into the cytosol and initiates a downstream caspase cascade, activating caspase-9 and subsequently caspase-3 (Li et al, 2019a). The mitochondrial membrane protein bcl-2, expressed prior to irreversible cellular damage, is a key anti-apoptosis factor (Scorrano et al, 2003;Li et al, 2019b).…”

Exosomes derived from smooth muscle cells ameliorate diabetes‐induced erectile dysfunction by inhibiting fibrosis and modulating the NO/cGMP pathway

“…To characterize the exosomes, protein levels of CD9 (1:1000; AF5139, Affinity Biosciences), CD63 (1:1000; AF5117, Affinity Biosciences), TSG101 (1:1000; DF8427, Affinity Biosciences) and calnexin (1:1000; AF5362, Affinity Biosciences) were analysed through Western blot analysis. The presence and morphology of exosomes were observed using transmission electron microscopy (TEM, FEI Company, Netherlands) 21 . The size distribution and concentration of the exosomes were determined by nanoparticle tracking analysis using a nanoparticle tracking video microscope (ZetaView, Particle Metrix, Germany) 22 …”