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Mechanisms of myostatin and activin A accumulation in chronic kidney disease
- Source :
- Nephrology Dialysis Transplantation, Nephrology Dialysis Transplantation, 2022, 37 (7), pp.1249-1260. ⟨10.1093/ndt/gfac136⟩
- Publication Year :
- 2022
- Publisher :
- HAL CCSD, 2022.
-
Abstract
- Background Myostatin and activin A induce muscle wasting by activating the ubiquitin proteasome system and inhibiting the Akt/mammalian target of rapamycin pathway. In chronic kidney disease (CKD), myostatin and activin A plasma concentrations are increased, but it is unclear if there is increased production or decreased renal clearance. Methods We measured myostatin and activin A concentrations in 232 CKD patients and studied their correlation with estimated glomerular filtration rate (eGFR). We analyzed the myostatin gene (MSTN) expression in muscle biopsies of hemodialysis (HD) patients. We then measured circulating myostatin and activin A in plasma and the Mstn and Inhba expression in muscles, kidney, liver and heart of two CKD mice models (adenine and 5/6 nephrectomy models). Finally, we analyzed whether the uremic toxin indoxyl sulfate (IS) increased Mstn expression in mice and cultured muscle cells. Results In patients, myostatin and activin A were inversely correlated with eGFR. MSTN expression was lower in HD patients’ muscles (vastus lateralis) than in controls. In mice with CKD, myostatin and activin A blood concentrations were increased. Mstn was not upregulated in CKD mice tissues. Inha was upregulated in kidney and heart. Exposure to IS did not induce Mstn upregulation in mouse muscles and in cultured myoblasts and myocytes. Conclusion During CKD, myostatin and activin A blood concentrations are increased. Myostatin is not overproduced, suggesting only an impaired renal clearance, but activin A is overproduced in the kidney and heart. We propose to add myostatin and activin A to the list of uremic toxins.
- Subjects :
- Mammals
Transplantation
muscle
[SDV]Life Sciences [q-bio]
musculoskeletal system
[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
Activins
sarcopenia
Mice
Nephrology
myostatin
Animals
Humans
activin A
Renal Insufficiency, Chronic
Muscle, Skeletal
indoxyl sulfate
Indican
chronic kidney disease
Subjects
Details
- Language :
- English
- ISSN :
- 09310509 and 14602385
- Database :
- OpenAIRE
- Journal :
- Nephrology Dialysis Transplantation, Nephrology Dialysis Transplantation, 2022, 37 (7), pp.1249-1260. ⟨10.1093/ndt/gfac136⟩
- Accession number :
- edsair.doi.dedup.....cc6be23fcf72085c600434b7074e5dcd