| First Author | Zhang L | Year | 2013 |
| Journal | Cell Metab | Volume | 18 |
| Issue | 3 | Pages | 368-79 |
| PubMed ID | 24011072 | Mgi Jnum | J:203817 |
| Mgi Id | MGI:5528776 | Doi | 10.1016/j.cmet.2013.07.012 |
| Citation | Zhang L, et al. (2013) Stat3 activation links a C/EBPdelta to myostatin pathway to stimulate loss of muscle mass. Cell Metab 18(3):368-79 |
| abstractText | 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 delta (C/EBPdelta) KO mice and C2C12 myotubes with knockdown of C/EBPdelta or myostatin, we determined that p-Stat3 initiates muscle wasting via C/EBPdelta, stimulating myostatin, a negative muscle growth regulator. C/EBPdelta KO also improved survival of CKD mice. We verified that p-Stat3, C/EBPdelta, and myostatin were increased in muscles of CKD patients. The pathway from p-Stat3 to C/EBPdelta to myostatin and muscle wasting could identify therapeutic targets that prevent muscle wasting. |
