领导这一研究的包括营养科学研究所的陈雁研究员和秦莹研究员，前者早年毕业于华西医科大学，1994年获得印第安纳大学医学和分子遗传系博士学位，2004年获中科院百人计划支持，2005年获国家基金委杰出青年，2006年入选“新世纪百千万人才工程”***人选，2007年获国务院政府特殊津贴，2007年为科技部重大科学计划**科学家。
TGF-b信号通路是细胞中关键的信号通路之一，影响了细胞的各种生命活动，包括细胞增殖、分化、凋亡等。以前的研究发现，在肺部炎症反应发生过程中，TGF-b信通路通过调控**细胞的功能对**的发**展行使了很大的作用。但TGF-b信号通路在呼吸道上皮细胞中的功能目前所知甚少。
在这篇文章中，研究人员成功构建了特异性在肺上皮细胞Clara细胞中表达Smad7的转基因小鼠模型，Smad7的过表达特异性抑制了Clara细胞中的TGF-b信号通路。通过与营养所秦莹课题组和巴斯德所孙兵课题组的合作研究，他们发现在卵白蛋白（OVA)诱导的急性**模型中该转基因小鼠显示明显的**缓解的表型，主要表现为呼吸道炎症减轻、粘液产生和胞质外基质沉积减少、以及OVA特异性**球蛋白减少。
进一步在肺组织匀浆检测多种细胞因子的表达发现多种细胞因子，包括白介素4（IL-4），白介素5（IL-5），白介素13（IL-13），白介素17（IL-17），白介素1（IL-1），白介素6（IL-6），粒细胞集落刺激因子（G-CSF），和巨噬细胞集落刺激因子（GM-CSF）在转基因小鼠中均有明显的下降，提示呼吸道上皮细胞中TGF-b信号通路的阻断可能抑制了**反应中上皮细胞和**细胞之间的通讯（crosstalk），继而导致炎症反应的降低。同时，在Smad7转基因小鼠模型中，乌拉坦（urethane）诱导的肺癌发生率明显高于对照组，提示在呼吸道上皮细胞中阻断TGF-b信号通路能够促进肺癌的发**展。这项研究**次运用体内模型阐释了在急性**和肺癌这两种常见的肺部病变中TGF-b信号通路在上皮细胞中所起的作用，进一步揭示了呼吸道上皮细胞中的TGF-b号通路不仅对于肺部炎症**的发**展过程，而且对肺部癌变的过程都发挥了关键的作用。
原文检索：
In vivo disruption of TGF-beta signaling by Smad7 in airwayepithelium alleviates allergic asthma but aggravates lungcarcinogenesis in mouse.AbstractBACKGROUND: TGF-beta has been postulated to play an important rolein the maintenance of epithelial homeostasis and the development ofepithelium-derived cancers. However, most of previous studies aremainly focused on the function of TGF-beta in immune cells to thedevelopment of allergic asthma and how TGF-beta signaling in airwayepithelium itself in allergic inflammation is largely unknown.Furthermore, the in vivo TGF-beta function specifically in theairway epithelium during lung cancer development has been largelyelusive. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the in vivocontribution of TGF-beta signaling in lung epithelium to thedevelopment of allergic disease and lung cancer, we generated atransgenic mouse model with Smad7, an intracellular inhibitor ofTGF-beta signaling, constitutively expressed in mouse airway Claracells using a mouse CC10 promoter. The mice were subjected to thedevelopment of OVA-induced allergic asthma and urethane-inducedlung cancer. The Smad7 transgenic animals significantly protectedfrom OVA-induced asthma, with reduced airway inflammation, airwaymucus production, extracellular matrix deposition, and productionof OVA-specific IgE. Further analysis of cytokine profiles in lunghomogenates revealed that the Th2 cytokines including IL-4, IL-5and IL-13, as well as other cytokines including IL-17, IL-1, IL-6,IP10, G-CSF, and GM-CSF were significantly reduced in thetransgenic mice upon OVA induction. In contrast, the Smad7transgenic animals had an increased incidence of lungcarcinogenesis when subjected to urethane treatment.CONCLUSION/SIGNIFICANCE: These studies, therefore, demonstrate forthe first time the in vivo function of TGF-beta signalingspecifically in airway epithelium during the development ofallergic asthma and lung cancer.