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Tumor necrosis factor‐α gene transfer induces cachexia and inhibits muscle regeneration
Author(s) -
Coletti Dario,
Moresi Viviana,
Adamo Sergio,
Molinaro Mario,
Sassoon David
Publication year - 2005
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.20160
Subject(s) - cachexia , myogenesis , tumor necrosis factor alpha , wasting , muscle atrophy , cytokine , skeletal muscle , biology , endocrinology , downregulation and upregulation , in vivo , medicine , cancer research , immunology , gene , cancer , genetics
Chronic disease states are associated with elevated levels of inflammatory cytokines that have been demonstrated to lead to severe muscle wasting. A mechanistic understanding of muscle wasting is hampered by limited in vivo cytokine models which can be applied to emerging mouse mutants as they are generated. We developed a simple and novel approach to induce adult mouse skeletal muscle wasting based on direct gene transfer of an expression vector encoding the secreted form of the murine tumor necrosis factor‐α (mTNFα). This procedure results in the production of elevated levels of circulating mTNFα followed by body weight loss, upregulation of Atrogin1, and muscle atrophy, including muscles distant from the site of gene transfer. We also found that mTNFα gene transfer resulted in a significant inhibition of regeneration following muscle injury. We conclude that in addition to being a potent inducer of cachexia, TNFα is a potent inhibitor of myogenesis in vivo. genesis 43:120–128, 2005. © 2005 Wiley‐Liss, Inc.