In Vivo Disruption of TGF-(beta) Signaling by Smad7 in Airway Epithelium Alleviates Allergic Asthma but Aggravates Lung Carcinogenesis in Mouse

	In Vivo Disruption of TGF-(beta) Signaling by Smad7 in Airway Epithelium Alleviates Allergic Asthma but Aggravates Lung Carcinogenesis in Mouse
	Luo, XL; Ding, QR; Wang, M; Li, ZG; Mao, KR; Sun, B; Pan, Y; Wang, ZZ; Zang, YQ; Chen, Y
刊名	PLOS ONE
	2010
卷号	5 期号:4 页码:e10149-e10149
通讯作者	Luo, XL (reprint author), Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China.,yqin@sibs.ac.cn ; ychen3@sibs.ac.cn
英文摘要	Background: TGF-beta has been postulated to play an important role in the maintenance of epithelial homeostasis and the development of epithelium-derived cancers. However, most of previous studies are mainly focused on the function of TGF-beta in immune cells to the development of allergic asthma and how TGF-beta signaling in airway epithelium itself in allergic inflammation is largely unknown. Furthermore, the in vivo TGF-beta function specifically in the airway epithelium during lung cancer development has been largely elusive. Methodology/Principal Findings: To evaluate the in vivo contribution of TGF-beta signaling in lung epithelium to the development of allergic disease and lung cancer, we generated a transgenic mouse model with Smad7, an intracellular inhibitor of TGF-beta signaling, constitutively expressed in mouse airway Clara cells using a mouse CC10 promoter. The mice were subjected to the development of OVA-induced allergic asthma and urethane-induced lung cancer. The Smad7 transgenic animals significantly protected from OVA-induced asthma, with reduced airway inflammation, airway mucus production, extracellular matrix deposition, and production of OVA-specific IgE. Further analysis of cytokine profiles in lung homogenates revealed that the Th2 cytokines including IL-4, IL-5 and IL-13, as well as other cytokines including IL-17, IL-1, IL-6, IP10, G-CSF, and GM-CSF were significantly reduced in the transgenic mice upon OVA induction. In contrast, the Smad7 transgenic animals had an increased incidence of lung carcinogenesis when subjected to urethane treatment. Conclusion/Significance: These studies, therefore, demonstrate for the first time the in vivo function of TGF-beta signaling specifically in airway epithelium during the development of allergic asthma and lung cancer.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	COLONY-STIMULATING FACTOR ; TGF-BETA ; T-CELLS ; INFLAMMATION ; CANCER ; MACROPHAGE ; EXPRESSION ; RECEPTOR ; HYPERRESPONSIVENESS ; INTERLEUKIN-10
收录类别	SCI
语种	英语
WOS记录号	WOS:000276706300006
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/986]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Luo, XL,Ding, QR,Wang, M,et al. In Vivo Disruption of TGF-(beta) Signaling by Smad7 in Airway Epithelium Alleviates Allergic Asthma but Aggravates Lung Carcinogenesis in Mouse[J]. PLOS ONE,2010,5(4):e10149-e10149.
APA	Luo, XL.,Ding, QR.,Wang, M.,Li, ZG.,Mao, KR.,...&Chen, Y.(2010).In Vivo Disruption of TGF-(beta) Signaling by Smad7 in Airway Epithelium Alleviates Allergic Asthma but Aggravates Lung Carcinogenesis in Mouse.PLOS ONE,5(4),e10149-e10149.
MLA	Luo, XL,et al."In Vivo Disruption of TGF-(beta) Signaling by Smad7 in Airway Epithelium Alleviates Allergic Asthma but Aggravates Lung Carcinogenesis in Mouse".PLOS ONE 5.4(2010):e10149-e10149.