Small Extracellular Vesicles Derived From Damaged Muscle Aggravate Kidney Injury Progression

Area of Science:

• Renal physiology and pathophysiology
• Skeletal muscle biology
• Extracellular vesicle biology

Background:

• Muscle atrophy is linked to kidney dysfunction in renal disease.
• The specific impact of skeletal muscle loss on kidney function remains unclear.
• This study investigates muscle-kidney crosstalk via muscle-derived extracellular vesicles (EVs) in kidney injury progression.

Purpose of the Study:

• To elucidate the role of muscle-derived EVs in kidney injury.
• To determine how muscle loss affects kidney inflammation and fibrosis.
• To explore the therapeutic potential of exercise-induced EVs in kidney disease.

Main Methods:

• Established a denervation-induced muscle loss model.
• Evaluated kidney injury markers in unilateral ureteral obstruction (UUO) and chronic kidney disease models.
• Utilized GW4869 to inhibit EV release and assessed EVs from denervated muscle, exercised muscle, and trained humans.

Main Results:

• Muscle denervation aggravated kidney injury, increasing albuminuria and inflammatory/fibrotic markers.
• Muscle-derived EVs from damaged muscle exacerbated kidney injury in vivo and in vitro.
• EVs from exercised muscle attenuated kidney fibrosis, partly via miR-21a-3p regulation.

Conclusions:

• Skeletal muscle loss contributes to kidney disease progression through muscle-derived EVs.
• Muscle-derived EVs, particularly their miRNA cargo like miR-21a-3p, play a critical role in kidney homeostasis.
• EVs from exercised muscle show promise in ameliorating kidney injury, suggesting therapeutic potential.