Tumor necrosis factor-alpha augments matrix metalloproteinase-9 production in skeletal muscle cells through the activation of transforming growth factor-beta-activated kinase 1 (TAK1)-dependent signaling pathway.

ABSTRACT: We have investigated the effect of tumor necrosis factor-alpha (TNF-alpha) on the production of extracellular matrix-degrading proteases in skeletal muscles. Using microarray, quantitative PCR, Western blotting, and zymography, we found that TNF-alpha drastically increases the production of matrix metalloproteinase (MMP)-9 from C2C12 myotubes. In vivo administration of TNF-alpha in mice increased the transcript level of MMP-9 in skeletal muscle tissues. Although TNF-alpha activated all the three MAPKs (i.e. ERK1/2, JNK, and p38), inhibition of ERK1/2 or p38 but not JNK blunted the TNF-alpha-induced production of MMP-9 from myotubes. Inhibition of Akt also inhibited the TNF-alpha-induced production of MMP-9. TNF-alpha increased the activation of transcription factors NF-kappaB and AP-1 but

SUBMITTER: Srivastava AK 

PROVIDER: S-EPMC4154379 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature