title: Apoptosis and myostatin mRNA are upregulated in the skeletal muscle of patients with chronic kidney disease.
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.
authors.affiliation: Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, Azienda Ospedale Università San Martino, Genoa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Verzola
authors.forename: Vanessa
authors.initials: V
authors.lastname: Procopio
authors.forename: Antonella
authors.initials: A
authors.lastname: Sofia
authors.forename: Barbara
authors.initials: B
authors.lastname: Villaggio
authors.forename: Alice
authors.initials: A
authors.lastname: Tarroni
authors.forename: Alice
authors.initials: A
authors.lastname: Bonanni
authors.forename: Irene
authors.initials: I
authors.lastname: Mannucci
authors.forename: Franco
authors.initials: F
authors.lastname: De Cian
authors.forename: Ezio
authors.initials: E
authors.lastname: Gianetta
authors.forename: Stefano
authors.initials: S
authors.lastname: Saffioti
authors.forename: Giacomo
authors.initials: G
authors.lastname: Garibotto
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D017209:Apoptosis; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007558:Italy; D048031:JNK Mitogen-Activated Protein Kinases / Q000032:analysis; D007674:Kidney Diseases / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009133:Muscular Atrophy / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D055435:Myostatin / Q000235:genetics*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis*; D017568:Rectus Abdominis / Q000737:chemistry* / Q000473:pathology*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C525911:MSTN protein, human; D055435:Myostatin; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases