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Cell Metab. 2013 Sep 3;18(3):368-79. doi: 10.1016/j.cmet.2013.07.012.

Stat3 activation links a C/EBPδ to myostatin pathway to stimulate loss of muscle mass.

Author information

1
Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: lipingz@bcm.edu.

Abstract

Catabolic conditions like chronic kidney disease (CKD) cause loss of muscle mass by unclear mechanisms. In muscle biopsies from CKD patients, we found activated Stat3 (p-Stat3) and hypothesized that p-Stat3 initiates muscle wasting. We created mice with muscle-specific knockout (KO) that prevents activation of Stat3. In these mice, losses of body and muscle weights were suppressed in models with CKD or acute diabetes. A small-molecule that inhibits Stat3 activation produced similar responses, suggesting a potential for translation strategies. Using CCAAT/enhancer-binding protein δ (C/EBPδ) KO mice and C2C12 myotubes with knockdown of C/EBPδ or myostatin, we determined that p-Stat3 initiates muscle wasting via C/EBPδ, stimulating myostatin, a negative muscle growth regulator. C/EBPδ KO also improved survival of CKD mice. We verified that p-Stat3, C/EBPδ, and myostatin were increased in muscles of CKD patients. The pathway from p-Stat3 to C/EBPδ to myostatin and muscle wasting could identify therapeutic targets that prevent muscle wasting.

PMID:
24011072
PMCID:
PMC3794464
DOI:
10.1016/j.cmet.2013.07.012
[Indexed for MEDLINE]
Free PMC Article

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