Small Extracellular Vesicles Derived From Damaged Muscle Aggravate Kidney Injury Progression

Authors
Songling Jiang, Seunghee Kang, Oran Kwon, Wonhyo Seo, Eun-Jung Jin, Hunjoo Ha, Joo Young Huh


Lab

Journal
Journal of Cachexia, Sarcopenia and Muscle

Abstract
Pathological events, including injury, atrophy and aging, can alter the cargo of muscle-derived EVs [31]. However, the mechanistic aspect of miRNAs as cargo in EVs from atrophic muscles has not been fully explained. Here, we identified miR-21-3p as potential cargo, and its role in muscle–kidney crosstalk was confirmed by the depletion of miR-21-3p from EVs derived from damaged myotubes. miR-21 is an established profibrotic miRNA [32], and its inhibition in muscle satellite cells from elderly mice reportedly exerts beneficial effects on myogenesis [33]. We also showed that exercise lowers the expression of miR-21a-3p levels in muscle, and plasma EVs derived from exercised subjects ameliorate kidney fibrosis, complementing the mechanisms involved in the beneficial effects of exercise [26]. miR-21 expression is induced in Duchenne muscular dystrophy and controls age-associated muscle fibrosis and dystrophy progression [34], while studies have also reported its involvement in kidney fibrosis [35]. Chau et al. identifiedPparαandMpvas key miR-21 targets involved in regulating lipid metabolism and mitochondrial reactive oxygen species generation. Here, miR-21-3p was selected as a target by screening forPpargc1a, which is also closely associated with lipid metabolism and mitochondria function in the kidneys [25]. miRNA biogenesis produces a guide (sense, miR-#-3p) and a passenger (antisense, miR-#-5p) strand. While the passenger strand was traditionally thought to be degraded, recent research showed it can also accumulate and regulate target mRNAs [36], sometimes exerting effects opposite to the guide strand [37]. We demonstrated for the first time that miR-21-3p is increased by muscle damage and negatively correlates withPpargc1aexpression, but whether miR-21-5p has similar effects warrants further research.

Keywords/Topics
extracellular vesicles; kidney injury; microRNA; muscle atrophy; muscle–kidney crosstalk

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcsm.13861

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