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microRNA-148a in Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Cardiomyocyte Apoptosis in Atrial Fibrillation by Inhibiting SMOC2

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Abstract

Exosomes-related microRNAs (miRNAs) have been considered to be the significant biomarkers contributing to the development of atrial fibrillation (AF). We observed the implicit mechanism of exosomes-miR-148a derived from bone marrow mesenchymal stem cells (BMSCs) in AF. The AF cell and mice models were established firstly. QRT-PCR and Western blot analysis were applied to detect the expression of miR-148a, SPARC-associated modular calcium-binding protein 2 (SMOC2), Bcl-2, Bax, and caspase-3. BMSCs were separated from healthy mice and exosomes were obtained from BMSCs. BMSCs were transfected with mimics and inhibitor, and HL-1 cells were treated with mimics and pcDNA3.1. MTT assay were used to detect cell viability of cells. Flow cytometric analysis and TUNEL analysis were used for detecting cell apoptosis of cells. In our study, exosomes derived from BMSCs inhibited the development of AF, and miR-148a acted a vital role in this segment. SMOC2 was a target gene of miR-148a and promoted apoptosis of HL-1 cells. Additionally, miR-148a mimics decreased cellular apoptosis, eliminated SMOC2 expression, and elevated Bcl-2 expression in AF-treated cells. Collectively, miR-148a overexpressed in BMSC-exosomes restrained cardiomyocytes apoptosis by inhibiting SMOC2.

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Data Availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

AF:

Atrial fibrillation

BMSCs:

Bone marrow mesenchymal stem cells

SPARC:

Secreted protein acidic and rich in cysteine

SMOC2:

SPARC-associated modular calcium-binding protein 2

Bcl-2:

B-cell CLL/lymphoma 2

Bax:

BCL2-associated X protein

MTT:

3-(4,5)-Dimethylthiahiazo(-z-y1)-3,5-di- phenytetrazoliumromide

mRNAs:

Messenger RNAs

miRNAs:

MicroRNAs

FBS:

Fetal bovine serum

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

ECL:

Enhanced chemiluminescence

qRT-PCR:

Quantitative real-time polymerase chain reaction

RIP:

RNA immunoprecipitation

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Authors and Affiliations

  1. Department of Cardiology, Xi’an No. 3 Hospital, the Affiliated Hospital Northwest University, Xi’an, Shanxi, 710018, P.R. China

    Weijuan Zhang

  2. Department of Cardiology, Jinan Central Hospital, Jinan, 250013, China

    Yilong Man

  3. Department of Emergency, Xi’an No. 3 Hospital, the Affiliated Hospital Northwest University, Xi’an, Shaanxi, 710018, P.R. China

    Zhanghu Chen

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WZ contributed to conception, design, and manuscript writing; WZ and YM performed the research; ZC involved in data analysis and interpretation; and all authors contributed to the final approval of the manuscript:

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Correspondence to Zhanghu Chen.

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The experimental protocol of our study was performed in accordance with the Guide for the Care and Use of Laboratory Animals and approved by Xi’an No.3 Hospital, the Affiliated Hospital Northwest University. The protocol of this research has been approved by the Ethics Committee of Xi’an No.3 Hospital, the Affiliated Hospital Northwest University. All patients have signed written informed consent. (IECAF20200501).

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Zhang, W., Man, Y. & Chen, Z. microRNA-148a in Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Cardiomyocyte Apoptosis in Atrial Fibrillation by Inhibiting SMOC2. Mol Biotechnol 64, 1076–1087 (2022). https://doi.org/10.1007/s12033-022-00487-z

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