The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy
Open accessAbstract
In response to stress, the heart undergoes extensive cardiac remodeling that results in cardiac fibrosis and pathological growth of cardiomyocytes (hypertrophy), which contribute to heart failure. Alterations in microRNA (miRNA) levels are associated with dysfunctional gene expression profiles associated with many cardiovascular disease conditions; however, miRNAs have emerged recently as paracrine signaling mediators. Thus, we investigated a potential paracrine miRNA crosstalk between cardiac fibroblasts and cardiomyocytes and found that cardiac fibroblasts secrete miRNA-enriched exosomes. Surprisingly, evaluation of the miRNA content of cardiac fibroblast-derived exosomes revealed a relatively high abundance of many miRNA passenger strands ("star" miRNAs), which normally undergo intracellular degradation. Using confocal imaging and coculture assays, we identified fibroblast exosomal-derived miR-21_3p (miR-21*) as a potent paracrine-acting RNA molecule that induces cardiomyocyte hypertrophy. Proteome profiling identified sorbin and SH3 domain-containing protein 2 (SORBS2) and PDZ and LIM domain 5 (PDLIM5) as miR-21* targets, and silencing SORBS2 or PDLIM5 in cardiomyocytes induced hypertrophy. Pharmacological inhibition of miR-21* in a mouse model of Ang II-induced cardiac hypertrophy attenuated pathology. These findings demonstrate that cardiac fibroblasts secrete star miRNA-enriched exosomes and identify fibroblast-derived miR-21* as a paracrine signaling mediator of cardiomyocyte hypertrophy that has potential as a therapeutic target.
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Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids
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MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
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Self-citationSecretory Mechanisms and Intercellular Transfer of MicroRNAs in Living Cells
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The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy
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Self-citationDistinct Mechanisms for MicroRNA Strand Selection by Drosophila Argonautes
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Loss of Enigma Homolog Protein Results in Dilated Cardiomyopathy
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“This is of interest, as cardiomyocyte-specific PDLIM5 knockout mice develop cardiomyopathy, suggesting PDLIM5 to play a major role in cardiac muscle structure and function (29).”
Cited by
Adipose-derived circulating miRNAs regulate gene expression in other tissues
Thomou, T., Mori, M. A., Dreyfuss, J. M., Konishi, M., Sakaguchi, M., Wolfrum, C., Rao, T. N., Winnay, J. N., Garcia-Martin, R., Grinspoon, S. K., et al. (2017) · Nature · doi:10.1038/nature21365 · Cited by 1,539
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Exosome-delivered microRNAs modulate the inflammatory response to endotoxin
Alexander, M., Hu, R., Runtsch, M. C., Kagele, D. A., Mosbruger, T. L., Tolmachova, T., Seabra, M. C., Round, J. L., Ward, D. M., & O’Connell, R. M. (2015) · Nature Communications · doi:10.1038/ncomms8321 · Cited by 769
Exosome Processing and Characterization Approaches for Research and Technology Development
Lai, J. J., Chau, Z. L., Chen, S., Hill, J. J., Korpany, K. V., Liang, N., Lin, L., Lin, Y., Liu, J. K., Liu, Y., et al. (2022) · Advanced Science · doi:10.1002/advs.202103222 · Cited by 623
Metadata
- Authors
- Bang, C., Batkai, S., Dangwal, S., Gupta, S. K., Foinquinos, A., Holzmann, A., Just, A., Remke, J., Zimmer, K., Zeug, A., Ponimaskin, E., Schmiedl, A., Yin, X., Mayr, M., Halder, R., Fischer, A., Engelhardt, S., Wei, Y., Schober, A., Fiedler, J., & Thum, T.
- Venue
- Journal of Clinical Investigation
- Published
- 2014-04-17
- Volume
- 124
- Issue
- 5
- Pages
- 2136-2146
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2109934828
- Cited by
- 979
- References
- 8
- FWCI
- 32.85
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Bang, C., Batkai, S., Dangwal, S., Gupta, S. K., Foinquinos, A., Holzmann, A., Just, A., Remke, J., Zimmer, K., Zeug, A., Ponimaskin, E., Schmiedl, A., Yin, X., Mayr, M., Halder, R., Fischer, A., Engelhardt, S., Wei, Y., Schober, A., . . . Thum, T. (2014). Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. Journal of Clinical Investigation. https://doi.org/10.1172/jci70577
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