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Journal Articles Nephrology Dialysis Transplantation Year : 2022

Mechanisms of myostatin and activin A accumulation in chronic kidney disease

Julien Aniort

Abstract

Myostatin and activin A induce muscle wasting by activating the ubiquitin proteasome system and inhibiting the Akt/mTOR pathway. In chronic kidney disease (CKD), myostatin and activin A plasma concentrations are increased, but it is not clear if there is an increased production or a 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 5/6th 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 up-regulated in CKD mice tissues. Inha was up-regulated in kidney and heart. Exposure to IS did not induce Mstn up-regulation in mice 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 over produced in kidney and heart. We propose to add myostatin and activin A to the list of uremic toxins.
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Dates and versions

hal-03670060 , version 1 (02-03-2023)

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Stanislas Bataille, Laetitia Dou, Marc Bartoli, Marion Sallée, Julien Aniort, et al.. Mechanisms of myostatin and activin A accumulation in chronic kidney disease. Nephrology Dialysis Transplantation, 2022, 37 (7), pp.1249-1260. ⟨10.1093/ndt/gfac136⟩. ⟨hal-03670060⟩
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