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RETRACTED ARTICLE: Exosomes derived from bone mesenchymal stem cells attenuate myocardial fibrosis both in vivo and in vitro via autophagy activation: the key role of miR-199a-3p/mTOR pathway

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Abstract

Autophagy suppression plays key a role during myocardial fibrosis (MF) progression. Exosomes from stem cells attenuate MF. The current study aimed to explain the antifibrosis effects of exosomes by focusing on microRNAs (miRs). MF was induced in rats using transverse aortic constriction (TAC) method and handled with exosomes from bone mesenchymal stem cells (BMSCs). The results of in vivo assays were verified with H9c2 cells. MiR expression profile was determined using microarray detection. The influence of miR-199a-3p modulation in vivo and in vitro on the antifibrosis effect of exosomes then was assessed. Exosomes attenuated MF by inhibiting inflammation, improving tissue structure, and inhibiting fibrosis-related indicators in TAC rats, and the effects were associated with autophagy activation. In H9c2 cells, exosomes suppressed cell viability, induced cell apoptosis, inhibited fibrosis-related indicators, while and the inhibition of autophagy by 3-MA would block the effect of exosomes. Based on the microarray detection, miR-199a-3p level was selected as therapeutic target. The inhibition of miR-199a-3p impaired the antifibrosis effects of exosomes on H9c2 cells, which was associated with autophagy inhibition. Collectively, exosomes from BMSCs exerted antifibrosis effects via the distant transfer of miR-199a-3p to heart tissues, which induced autophagy by inhibiting mTOR.

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  1. Department of Cardiology, The First People’s Hospital of Wenling, No. 333 Chuan’an South Road, Chengxi Street, Wenling, 317500, Zhejiang, China

    Chenrong Fan, Qizeng Wang, Youjin Chen, Tingting Ye & Yuncao Fan

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Correspondence to Yuncao Fan.

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All the animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Shenyang Bioinform Company (China) (approval no. 20200111) and were carried out in accordance with international guidelines for care and use of laboratory animals.

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This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1007/s13577-022-00761-x

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Fan, C., Wang, Q., Chen, Y. et al. RETRACTED ARTICLE: Exosomes derived from bone mesenchymal stem cells attenuate myocardial fibrosis both in vivo and in vitro via autophagy activation: the key role of miR-199a-3p/mTOR pathway. Human Cell 35, 817–835 (2022). https://doi.org/10.1007/s13577-022-00680-x

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