Exogenous miR-26a suppresses muscle wasting and renal fibrosis in obstructive kidney disease
Aiqing Zhang1,2, Haidong Wang2,3, Bin Wang2,4
1Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Abstract:
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 α-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.
Insights
Exogenous microRNA (miR)-26a delivered via exosomes ameliorates muscle wasting and kidney fibrosis in obstructive kidney disease models. This exosome-mediated therapy shows promise for treating these interconnected conditions.
Area of Science:
- Biomedical Science
- Molecular Biology
- Regenerative Medicine
Background:
- Chronic kidney disease frequently leads to kidney fibrosis.
- Muscle wasting is a common comorbidity in obstructive kidney disease.
- MicroRNA (miR)-26a levels are reduced in kidney and muscle tissues affected by obstructive kidney disease.
Purpose of the Study:
- To investigate the therapeutic potential of exogenous miR-26a delivered by exosomes.
- To determine if miR-26a can suppress renal fibrosis and muscle wasting in a mouse model of obstructive kidney disease.
Main Methods:
- Exosomes were engineered to encapsulate miR-26a.
- Exosome-miR-26a was injected into the skeletal muscle of mice with unilateral ureteral obstruction (UUO).
- Muscle weights, myostatin levels, and renal fibrosis markers (α-smooth muscle actin, Masson's trichrome, CTGF, TGF-β1) were assessed.
Main Results:
- Exosome-miR-26a injection increased miR-26a expression in serum exosomes and ameliorated muscle wasting in UUO mice.
- miR-26a intervention reduced renal fibrosis, decreased connective tissue growth factor (CTGF) and TGF-β1 protein levels in the kidney.
- Exogenous miR-26a inhibited the transcription factor forkhead box O1, preventing muscle atrophy, and directly suppressed CTGF, limiting renal fibrosis.
Conclusions:
- Exosomes carrying miR-26a demonstrate a therapeutic effect on both muscle atrophy and renal fibrosis in obstructive kidney disease.
- This exosome-mediated delivery of miR-26a offers a potential therapeutic strategy for managing the dual complications of muscle wasting and kidney fibrosis.
