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Exogenous miR‐26a suppresses muscle wasting and renal fibrosis in obstructive kidney disease

Kidney fibrosis occurs in almost every type of chronic kidney disease. We found that microRNA (miR)‐26a was decreased in the kidney, muscle, and exosomes of unilateral ureteral obstruction (UUO) mice. We hypothesized that exogenous miR‐26 could suppresses renal fibrosis and muscle wasting in obstructive kidney disease. For this purpose, we generated exosomes that encapsulated miR‐26, then injected these into skeletal muscle of UUO mice. The expression of miR‐26a was elevated in serum exosomes from UUO mice following exosome‐miR‐26a injection. In these mice, muscle wasting has been ameliorated as evidenced by increased muscle weights. In addition, a muscle atrophy marker, myostatin, is increased in UUO muscle; provision of miR‐26a abolished this increase. We detected a remote effect of exosomes containing miR‐26a in UUO‐induced renal fibrosis. The intervention of miR‐26a attenuated UUO‐induced renal fibrosis as determined by immunohistological assessment of a‐smooth muscle actin and Masson's trichrome staining. Furthermore, exogenous miR‐26a decreased the protein levels of 2 profibrosis proteins, connective tissue growth factor (CTGF) and TGF‐β1, in UUO kidney. Our data showed that exosomes containing miR‐26a prevented muscle atrophy by inhibiting the transcription factor forkhead box O1. Likewise, the exosome‐carried miR‐26a limited renal fibrosis by directly suppressing CTGF. Our findings provide an experimental basis for exosome‐mediated therapy of muscle atrophy and renal fibrosis.—Zhang, A., Wang, H., Wang, B., Yuan, Y., Klein, J. D., Wang, X. H. Exogenous miR‐26a suppresses muscle wasting and renal fibrosis in obstructive kidney disease. FASEB J. 33, 13590‐13601 (2019). www.fasebj.org