Abstract
MicroRNAs (miRNAs) play a key role in various pathological processes like atrial fibrillation (AF). However, the mechanisms remain unclear. Herein, this study was undertaken to probe the roles of ADAM10 and its targeting miR-520d in rapid pacing-induced apoptosis in atrial myocytes. In this study, the atrial myocytes grew adherently with irregular morphology. Immunofluorescence showed that more than 90% of atrial myocytes were α-sarcomeric actin (α-SCA) positive, indicating that the primary cells were positive for α-SCA staining and atrial myocytes were successfully isolated. The pacing atrial myocyte model was established after rapid pacing stimulation and we found the rapid pacing stimulation caused elevated ADAM10 and suppressed miR-520d. CCK-8 assay was applied for evaluation of cell viability, TUNEL staining for assessment of cell apoptosis and dual-luciferase reporter gene assay for verification of the targeting relationship between miR-520d and ADAM10. Overexpression of miR-520d or silencing of ADAM10 could enhance cell viability and reduce cell apoptosis in the rapid pacing-induced atrial myocytes. ADAM10 was a target gene of miR-520d. MiR-520d negatively targeted ADAM10, thereby promoting cell viability and inhibiting apoptosis in rapid pacing atrial myocyte model. In summary, miR-520d enhances atrial myocyte viability and inhibits cell apoptosis in rapid pacing-induced AF mouse model through negative mediation of ADAM10.
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This study was funded by the grant from the National Youth Natural Science Foundation of China (Grant No. 81800056).
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FQH and PHW conceived the ideas. TY and PJQ designed the experiments. HJ and ZQC performed the experiments. YSL analyzed the data. ZZF and HJ provided critical materials. FQH and PJQ wrote the manuscript. FQH and PHW supervised the study. All the authors have read and approved the final version for publication.
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Fu, Q., Tang, Y., Peng, J. et al. miR-520d suppresses rapid pacing-induced apoptosis of atrial myocytes through mediation of ADAM10. J Mol Histol 52, 207–217 (2021). https://doi.org/10.1007/s10735-020-09938-w
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DOI: https://doi.org/10.1007/s10735-020-09938-w