Premium
Glucocorticoids reduce muscle atrophy‐related microRNAs via exosomal microRNA packaging (1163.4)
Author(s) -
Hudson Matthew,
WoodworthHobbs Myra,
Rahnert Jill,
Zheng Bin,
Price S.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1163.4
Subject(s) - myogenesis , microvesicles , exosome , microrna , intracellular , muscle atrophy , c2c12 , endocrinology , glucocorticoid , medicine , myocyte , atrophy , chemistry , microbiology and biotechnology , biology , skeletal muscle , biochemistry , gene
Several microRNAs, including miR‐23a and miR‐182, participate in skeletal muscle atrophy by regulating the level of key atrophy‐inducing proteins. We recently found that the intracellular levels of these microRNAs are reduced in C2C12 myotubes within 1‐2 hours of addition of the glucocorticoid dexamethasone (Dex). The purpose of this study was to investigate the mechanism underlying the rapid decrease in the intracellular levels of these microRNAs. We tested the hypothesis that miR‐23a and miR‐182 are incorporated into exosomes and exported from myotubes following glucocorticoid treatment. Administration of Dex (1µM) to C2C12 myotubes for 6 h in exosome‐free culture media resulted in decreased intracellular miR‐23a and miR‐182. Isolation and quantitation of exosomal miR‐23a and miR‐182 from media revealed an increase in both microRNAs. Interestingly, the total number of exosomes in the culture media of control and Dex‐treated cells was not different indicating Dex did not increase exosome export. Levels of miR‐23a and miR‐182 were decreased in gastrocnemius muscle of rats undergoing atrophy due to streptozotocin‐induced diabetes. MiR‐23a and miR‐182 in urinary exosomes from diabetic rats were also reduced, suggesting that their levels in urine reflect the levels in muscle during the persistent atrophic state. These findings identify a novel mechanism by which muscle can rapidly reduce the level of intracellular microRNAs, and demonstrate that exosomal microRNA packaging is a specific and highly regulated process. Grant Funding Source : Supported by NIH T32 DK007656 (MBH) and NIH DK95610, VA Merit X01BX001456 (SRP)