miR-23a is decreased during muscle atrophy by a mechanism that includes calcineurin signaling and exosome-mediated export
Open accessAbstract
Skeletal muscle atrophy is prevalent in chronic diseases, and microRNAs (miRs) may play a key role in the wasting process. miR-23a was previously shown to inhibit the expression of atrogin-1 and muscle RING-finger protein-1 (MuRF1) in muscle. It also was reported to be regulated by cytoplasmic nuclear factor of activated T cells 3 (NFATc3) in cardiomyocytes. The objective of this study was to determine if miR-23a is regulated during muscle atrophy and to evaluate the relationship between calcineurin (Cn)/NFAT signaling and miR-23a expression in skeletal muscle cells during atrophy. miR-23a was decreased in the gastrocnemius of rats with acute streptozotocin-induced diabetes, a condition known to increase atrogin-1 and MuRF1 expression and cause atrophy. Treatment of C2C12 myotubes with dexamethasone (Dex) for 48 h also reduced miR-23a as well as RCAN1.4 mRNA, which is transcriptionally regulated by NFAT. NFATc3 nuclear localization and the amount of miR-23a decreased rapidly within 1 h of Dex administration, suggesting a link between Cn signaling and miR-23a. The level of miR-23a was lower in primary myotubes from mice lacking the α- or β-isoform of the CnA catalytic subunit than wild-type mice. Dex did not further suppress miR-23a in myotubes from Cn-deficient mice. Overexpression of CnAβ in C2C12 myotubes prevented Dex-induced suppression of miR-23a. Finally, miR-23a was present in exosomes isolated from the media of C2C12 myotubes, and Dex increased its exosomal abundance. Dex did not alter the number of exosomes released into the media. We conclude that atrophy-inducing conditions downregulate miR-23a in muscle by mechanisms involving attenuated Cn/NFAT signaling and selective packaging into exosomes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Treatment of C2C12 myotubes with dexamethasone for 48 h reduces intracellular miR-23a and increases its ELV-MT abundance.
“treatment of C2C12 myotubes with dexamethasone for 48 h reduced the intracellular level of miR-23a but increased its ELV-MT abundance.”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Hudson et al., 2014
Atrophy-inducing conditions lead to selective packaging of miRNAs into ELV-MT.
“these data suggested that atrophy-inducing conditions lead to a selective packaging of miRNAs into ELV-MT”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Hudson et al., 2014
Dexamethasone does not alter the number of ELVs released.
“dexamethasone did not alter the number of ELVs released”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Hudson et al., 2014
This changes the delivered message to recipient cells.
“thus changing the delivered message to recipient cells.”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Hudson et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714 · see citing works
Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007) · Nature Cell Biology · doi:10.1038/ncb1596 · Cited by 12,834 · see citing works
Circulating microRNAs as stable blood-based markers for cancer detection
Mitchell, P. S., Parkin, R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan, E. L., Peterson, A., Noteboom, J., O'Briant, K. C., Allen, A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804549105 · Cited by 7,969 · see citing works
Membrane vesicles as conveyors of immune responses
Théry, C., Ostrowski, M., & Segura, É. (2009) · Nature reviews. Immunology · doi:10.1038/nri2567 · Cited by 3,869 · see citing works
Identification of ubiquitin ligases required for skeletal muscle atrophy.
Bodine, S. C., Latres, E., Baumhueter, S., Lai, V. K.-M., Nunez, L., Clarke, B. A., Poueymirou, W. T., Panaro, F. J., Na, E., Dharmarajan, K., et al. (2001) · Science · doi:10.1126/science.1065874 · Cited by 3,521 · see citing works
Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy
Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A., & Goldberg, A. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251541198 · Cited by 1,774 · see citing works
Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression
Lecker, S. H., Jagoe, R. T., Gilbert, A., Gomes, M., Baracos, V., Bailey, J., Price, S. R., Mitch, W. E., & Goldberg, A. L. (2004) · The FASEB Journal · doi:10.1096/fj.03-0610com · Cited by 1,539 · see citing works
Self-citationMechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes.
Montecalvo, A., Larregina, A. T., Shufesky, W. J., Beer Stolz, D., Sullivan, M. L. G., Karlsson, J. M., Baty, C. J., Gibson, G. A., Erdos, G., Wang, Z., et al. (2012) · Blood · doi:10.1182/blood-2011-02-338004 · Cited by 1,262 · see citing works
Protein degradation by the ubiquitin-proteasome pathway in normal and disease states
Lecker, S. H., Goldberg, A. L., & Mitch, W. E. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006010083 · Cited by 1,234 · see citing works
The Molecular Basis of Skeletal Muscle Atrophy
Jackman, R. W., & Kandarian, S. C. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00579.2003 · Cited by 1,008 · see citing works
Calcineurin/NFAT Coupling Participates in Pathological, but not Physiological, Cardiac Hypertrophy
Wilkins, B. J., Dai, Y., Bueno, O. F., Parsons, S. A., Xu, J., Plank, D. M., Jones, F. S., Kimball, T. R., & Molkentin, J. D. (2003) · Circulation Research · doi:10.1161/01.res.0000109415.17511.18 · Cited by 762 · see citing works
The Long and Short of MicroRNA
Yates, L. A., Norbury, C. J., & Gilbert, R. J. C. (2013) · Cell · doi:10.1016/j.cell.2013.04.003 · Cited by 706 · see citing works
Sacheck, J. M., Hyatt, J. K., Raffaello, A., Thomas Jagoe, R., Roy, R. R., Reggie Edgerton, V., Lecker, S. H., & Goldberg, A. L. (2007) · The FASEB Journal · doi:10.1096/fj.06-6604com · Cited by 585 · see citing works
Li, H., Kedar, V., Zhang, C., McDonough, H., Arya, R., Wang, D.-Z., & Patterson, C. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22220 · Cited by 430 · see citing works
miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy
Lin, Z., Murtaza, I., Wang, K., Jiao, J., Gao, J., & Li, P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811371106 · Cited by 360 · see citing works
Price, S. R., Bailey, J. L., Wang, X., Jurkovitz, C. T., England, B. K., Ding, X., Phillips, L. S., & Mitch, W. E. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118968 · Cited by 348 · see citing works
Self-citationC2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction
Guescini, M., Guidolin, D., Vallorani, L., Casadei, L., Gioacchini, A. M., Tibollo, P., Battistelli, M., Falcieri, E., Battistin, L., Agnati, L. F., et al. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.04.006 · Cited by 294 · cited 2× · see citing works
“In 2010, it was reported that C2C12 myotubes release exosomes, but there was no attempt to measure or identify the encapsulated microRNAs (11).”
P38 MAPK Links Oxidative Stress to Autophagy-Related Gene Expression in Cachectic Muscle Wasting
McClung, J. M., Judge, A. R., Powers, S. K., & Yan, Z. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00192.2009 · Cited by 277 · see citing works
Russell, A. P., Lamon, S., Boon, H., Wada, S., Güller, I., Brown, E. L., Chibalin, A., Zierath, J. R., Snow, R. J., Stepto, N. K., et al. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.255695 · Cited by 272 · see citing works
Li, H., Willis, M. S., Lockyer, P. P., Miller, N., McDonough, H., Glass, D. J., & Patterson, C. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31757 · Cited by 247 · see citing works
Impaired cardiac hypertrophic response in Calcineurin Aβ -deficient mice
Bueno, O. F., Wilkins, B. J., Tymitz, K. M., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.072647999 · Cited by 241 · see citing works
Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting
Mitch, W. E., Bailey, J. L., Wang, X., Jurkovitz, C. T., Newby, D. E., & Price, S. R. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.276.5.c1132 · Cited by 237 · see citing works
Self-citationOxidative stress and disuse muscle atrophy
Powers, S. K., Smuder, A. J., & Judge, A. R. (2012) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328352b4c2 · Cited by 234 · see citing works
Russell, A. P., Wada, S., Vergani, L., Hock, M. B., Lamon, S., Léger, B., Ushida, T., Cartoni, R., Wadley, G. D., Hespel, P., et al. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.08.015 · Cited by 224 · see citing works
Hudson, M. B., Smuder, A. J., Nelson, W. B., Bruells, C. S., Levine, S., & Powers, S. K. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e31823c8cc9 · Cited by 206 · see citing works
Self-citationWada, S., Kato, Y., Okutsu, M., Miyaki, S., Suzuki, K., Yan, Z., Schiaffino, S., Asahara, H., Ushida, T., & Akimoto, T. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.271270 · Cited by 200 · see citing works
Renaming the DSCR1 / Adapt78 gene family as RCAN : regulators of calcineurin
Davies, K. J. A., Ermak, G., Rothermel, B. A., Pritchard, M. A., Heitman, J., Ahnn, J., Henrique‐Silva, F., Crawford, D. R., Canaider, S., Strippoli, P., et al. (2007) · The FASEB Journal · doi:10.1096/fj.06-7246com · Cited by 168 · see citing works
T cell responses in calcineurin A alpha-deficient mice.
Zhang, B. W., Zimmer, G., Chen, J., Ladd, D., Li, E., Alt, F. W., Wiederrecht, G., Cryan, J. G., O’Neill, E. A., Seidman, C. E., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.2.413 · Cited by 150 · see citing works
Dehoux, M., Beneden, R. V., Pasko, N., Lause, P., Verniers, J., Underwood, L. E., Ketelslegers, J., & Thissen, J. (2004) · Endocrinology · doi:10.1210/en.2004-0406 · Cited by 147 · see citing works
Zheng, B., Ohkawa, S., Li, H., Roberts‐Wilson, T. K., & Price, S. R. (2010) · The FASEB Journal · doi:10.1096/fj.09-151480 · Cited by 145 · see citing works
Self-citationJansen, F., Yang, X., Hoyer, F. F., Paul, K., Heiermann, N., Becher, M. U., Hussein, N. S. A., Kebschull, M., Bedorf, J., Franklin, B. S., et al. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.253229 · Cited by 134 · see citing works
Kukreti, H., Amuthavalli, K., Harikumar, A., Sathiyamoorthy, S., Feng, P. Z., Anantharaj, R., Tan, S. L. K., Lokireddy, S., Bonala, S., Sriram, S., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.390369 · Cited by 121 · see citing works
Allen, D. L., & Loh, A. S. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00142.2010 · Cited by 111 · see citing works
Decreased miR-29 Suppresses Myogenesis in CKD
Wang, X. H., Hu, Z., Klein, J. D., Zhang, L., Fang, F., & Mitch, W. E. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010121278 · Cited by 110 · see citing works
Qiu, S., Huang, D., Yin, D., Li, F., Li, X., Kung, H., & Peng, Y. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.015 · Cited by 107 · see citing works
Post-transcriptional Stimulation of Gene Expression by MicroRNAs
Lee, S., & Vasudevan, S. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-5107-5_7 · Cited by 104 · see citing works
Friday, B. B., & Pavlath, G. K. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.2.303 · Cited by 102 · see citing works
Mannose receptor regulates myoblast motility and muscle growth
Jansen, K. M., & Pavlath, G. K. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200601102 · Cited by 93 · see citing works
Calcineurin: A poorly understood regulator of muscle mass
Hudson, M. B., & Price, S. R. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.06.029 · Cited by 67 · see citing works
Self-citationCalcineurin signaling and PGC-1α expression are suppressed during muscle atrophy due to diabetes
Roberts‐Wilson, T. K., Reddy, R. N., Bailey, J. L., Zheng, B., Ordas, R. J., Gooch, J. L., & Price, S. R. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.03.019 · Cited by 56 · see citing works
Self-citationMuscle Atrophy in Chronic Kidney Disease Results From Abnormalities in Insulin Signaling
Price, S. R., Gooch, J. L., Donaldson, S., & Roberts‐Wilson, T. K. (2010) · Journal of Renal Nutrition · doi:10.1053/j.jrn.2010.05.007 · Cited by 54 · see citing works
Self-citationIdentification of microRNAs involved in dexamethasone-induced muscle atrophy
Shen, H., Liu, T., Fu, L., Zhao, S., Fan, B., Cao, J., & Li, X. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1692-9 · Cited by 46 · see citing works
Cell and Molecular Regulation of Endothelin-1 Production during Hepatic Wound Healing
Shao, R., Shi, Z., Gotwals, P. J., Koteliansky, V., George, J., & Rockey, D. C. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.02-06-0093 · Cited by 46 · see citing works
Validation of the isolation and quantification of kidney enriched miRNAs for use as biomarkers
Sharkey, J. W., Antoine, D. J., & Park, B. K. (2012) · Biomarkers · doi:10.3109/1354750x.2012.657246 · Cited by 29 · see citing works
Calcineurin A-β is required for hypertrophy but not matrix expansion in the diabetic kidney
Reddy, R. N., Knotts, T., Roberts, B. R., Molkentin, J. D., Price, S. R., & Gooch, J. L. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00910.x · Cited by 21 · see citing works
Self-citationJabr, R. I., Wilson, A. J., Riddervold, M. H., et al. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00139.2005 · Cited by 21 · see citing works
Ying, S., Chang, D. C., & Lin, S.-L. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-083-0_1 · Cited by 18 · see citing works
Megarole for MicroRNA in Muscle Disease
Crist, C. G., & BUCKINGHAM, M. E. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.10.007 · Cited by 13 · see citing works
[Effects of oxidative stress on MuRF1 expression in skeletal muscle of diabetic rats].
Chen, G., Lü, K.-R., Yang, Y., et al. (2011) · PubMed · Cited by 6 · see citing works
Fry, C. S. (2014) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00022.2014 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Muscle releases alpha-sarcoglycan positive extracellular vesicles carrying miRNAs in the bloodstream
Guescini, M., Canonico, B., Lucertini, F., Maggio, S., Annibalini, G., Barbieri, E., Luchetti, F., Papa, S., & Stocchi, V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125094 · Cited by 228 · see citing works
“Furthermore, two key studies from separate groups have recently shown that muscle cells release exosomes carrying bio-active miRNAs [47,48].”
BackgroundThe role of extracellular vesicles in skeletal muscle and systematic adaptation to exercise
Vechetti, I. J., Valentino, T., Mobley, C. B., & McCarthy, J. J. (2021) · The Journal of Physiology · doi:10.1113/jp278929 · Cited by 141 · see citing works
Skeletal Muscle-Released Extracellular Vesicles: State of the Art
Rome, S., Forterre, A., Mizgier, M. L., & Bouzakri, K. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00929 · Cited by 139 · see citing works
Delphinidin Prevents Muscle Atrophy and Upregulates miR-23a Expression
Murata, M., Nonaka, H., Komatsu, S., Goto, M., Morozumi, M., Yamada, S., Lin, I.-C., Yamashita, S., & Tachibana, H. (2017) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6b03661 · Cited by 47 · see citing works
Hormones, Metabolism and the Benefits of Exercise
(2017) · Research and Perspectives in Endocrine Interactions · doi:10.1007/978-3-319-72790-5 · Cited by 44 · see citing works
Hernandez-Torres, F., Aranega, A. E., & Franco, D. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.07.009 · Cited by 36 · see citing works
- Authors
- Hudson, M. B., Woodworth-Hobbs, M. E., Zheng, B., Rahnert, J. A., Blount, M. A., Gooch, J. L., Searles, C. D., & Price, S. R.
- Affiliations
- Emory University (US)
- Nutrition and Health Sciences, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia;
- Corresponding author
- Hudson, Matthew B.
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2014-03-15
- Volume
- 306
- Issue
- 6
- Pages
- C551-C558
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- PMC
- PMC3948973
- OpenAlex
- W2168020094
- Cited by
- 137
- References
- 50
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 12 · 2020: 18 · 2019: 12 · 2018: 13 · 2017: 16 · 2016: 13 · 2015: 14 · 2014: 6
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - PCOM (Philadelphia College of Osteopathic Medicine) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01‐BX001456)
- National Heart, Lung, and Blood Institute (HL-109559, R01HL109559)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-007656, T32DK007734, R01DK095610, T32DK007656)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-23a, skeletal muscle atrophy, calcineurin signaling, NFATc3, exosomes, dexamethasone, streptozotocin-induced diabetes, atrogin-1, MuRF1, RCAN1.4, microRNA regulation, gastrocnemius
- MeSH terms
- Animals, Biological Transport, Calcium-Binding Proteins, Cells, Cultured, Dexamethasone, Diabetes Mellitus, Experimental, Male, Muscle Proteins, Muscular Atrophy, RNA, Messenger, Streptozocin, Signal Transduction, Rats, Sprague-Dawley, Mice, Knockout, Muscle Fibers, Skeletal, Calcineurin, MicroRNAs, Intracellular Signaling Peptides and Proteins, NFATC Transcription Factors, Mice, Rats, Exosome Multienzyme Ribonuclease Complex
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
