Apoptosis and myostatin mRNA are upregulated in the skeletal muscle of patients with chronic kidney disease

Daniela Verzola, Vanessa Procopio, Antonella Sofia, Barbara Villaggio, Alice Tarroni, Alice Bonanni, Irene Mannucci, Franco De Cian, Ezio Gianetta, Stefano Saffioti, Giacomo Garibotto

Research output: Contribution to journalArticlepeer-review

Abstract

Apoptosis and myostatin are major mediators of muscle atrophy and might therefore be involved in the wasting of uremia. To examine whether they are expressed in the skeletal muscle of patients with chronic kidney disease (CKD), we measured muscle apoptosis and myostatin mRNA and their related intracellular signal pathways in rectus abdominis biopsies obtained from 22 consecutive patients with stage 5 CKD scheduled for peritoneal dialysis. Apoptotic loss of myonuclei, determined by anti-single-stranded DNA antibody and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays, was significantly increased three to fivefold, respectively. Additionally, myostatin and interleukin (IL)-6 gene expressions were significantly upregulated, whereas insulin-like growth factor-I mRNA was significantly lower than in controls. Phosphorylated JNK (c-Jun amino-terminal kinase) and its downstream effector, phospho-c-Jun, were significantly upregulated, whereas phospho-Akt was markedly downregulated. Multivariate analysis models showed that phospho-Akt and IL-6 contributed individually and significantly to the prediction of apoptosis and myostatin gene expression, respectively. Thus, our study found activation of multiple pathways that promote muscle atrophy in the skeletal muscle of patients with CKD. These pathways appear to be associated with different intracellular signals, and are likely differently regulated in patients with CKD.

Original languageEnglish
Pages (from-to)773-782
Number of pages10
JournalKidney International
Volume79
Issue number7
DOIs
Publication statusPublished - Apr 2011

Keywords

  • Akt
  • apoptosis
  • chronic renal disease
  • myostatin
  • protein-energy wasting

ASJC Scopus subject areas

  • Nephrology

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