Involvement of Skeletal Muscle Gene Regulatory Network in Susceptibility to Wound Infection Following Trauma
Involvement of Skeletal Muscle Gene Regulatory Network in Susceptibility to Wound Infection Following Trauma
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DOI：
10.1371/journal.pone.0001356
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发表时间：
2007-12-26
期刊：
影响因子：
3.7
通讯作者：
Rahme, Laurence G.
中科院分区：
文献类型：
--
作者：
Apidianakis, Yiorgos;Mindrinos, Michael N.;Rahme, Laurence G.
尽管我们对创伤的病理生理学的理解有了新的进展，但创伤患者感染易感性的基础仍然不清楚。黑腹果蝇/铜绿假单胞菌损伤和感染模型被用来确定宿主的遗传成分，导致感染的高度易感性，严重创伤。我们发现，铜绿假单胞菌损害骨骼肌基因（SMG）的表达在损伤部位，以促进感染。我们证明SMG结构组分的激活是在cJun-N-末端激酶（JNK）激酶，半翅目（Hep）的控制下，并且该途径的激活促进了果蝇和小鼠中对铜绿假单胞菌的局部抗性。我们的研究将SMG的表达和功能与感染易感性增加联系起来，并表明铜绿假单胞菌通过限制受损骨骼肌组织中SMG的表达来局部影响SMG的稳态。这些宿主反应的局部增强和/或毒性铜绿假单胞菌细胞对其抑制的抑制可以导致预防或治疗严重受伤个体中的有害和潜在致命感染的新疗法。
Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals.