Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease.
Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease.
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DOI：
10.1371/journal.pone.0070196
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sorscher EJ
中科院分区：
文献类型：
--
作者：
Harris WT;Kelly DR;Zhou Y;Wang D;MacEwen M;Hagood JS;Clancy JP;Ambalavanan N;Sorscher EJ
TGF-β 是肺纤维化的介质，是 CF 呼吸恶化的遗传修饰剂。 TGF-β信号传导与 CF 肺病之间的机制关系尚未确定。研究 CF 肺组织中肌成纤维细胞分化作为一种新途径，TGF-β 信号传导可能通过该途径导致肺功能衰退、气道重塑和组织纤维化。对来自 CF 和非 CF 受试者的肺样本进行形态测定，分析总 TGF-β1、TGF-β 信号传导（Smad2 磷酸化）、肌成纤维细胞分化（α-平滑肌肌动蛋白）和胶原沉积（Masson 三色染色）。 CF 中的 TGF-β 信号传导和纤维化显着增加 (p<0.01)，并且 CF 中肌成纤维细胞的存在量是正常肺组织的四倍 (p<0.005)。在具有显着 TGF-β 信号传导的肺组织中，肌成纤维细胞分化和组织纤维化均显着增强 (p<0.005)。这些研究首次证实，先前描述的肺纤维化的致病机制在囊性纤维化肺病中也很突出。 CF 中显着的肌成纤维细胞增殖和纤维化区域存在 TGF-β 依赖性信号传导，这表明正在开发的针对其他促纤维化肺部疾病的策略也可用于 CF 的评估。
TGF-β, a mediator of pulmonary fibrosis, is a genetic modifier of CF respiratory deterioration. The mechanistic relationship between TGF-β signaling and CF lung disease has not been determined. To investigate myofibroblast differentiation in CF lung tissue as a novel pathway by which TGF-β signaling may contribute to pulmonary decline, airway remodeling and tissue fibrosis. Lung samples from CF and non-CF subjects were analyzed morphometrically for total TGF-β1, TGF-β signaling (Smad2 phosphorylation), myofibroblast differentiation (α-smooth muscle actin), and collagen deposition (Masson trichrome stain). TGF-β signaling and fibrosis are markedly increased in CF (p<0.01), and the presence of myofibroblasts is four-fold higher in CF vs. normal lung tissue (p<0.005). In lung tissue with prominent TGF-β signaling, both myofibroblast differentiation and tissue fibrosis are significantly augmented (p<0.005). These studies establish for the first time that a pathogenic mechanism described previously in pulmonary fibrosis is also prominent in cystic fibrosis lung disease. The presence of TGF-β dependent signaling in areas of prominent myofibroblast proliferation and fibrosis in CF suggests that strategies under development for other pro-fibrotic lung conditions may also be evaluated for use in CF.
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影响因子：
3.1
作者：
Harris, William T.;Muhlebach, Marianne S.;Oster, Robert A.;Knowles, Michael R.;Clancy, J. P.;Noah, Terry L.
通讯作者：
Noah, Terry L.
影响因子：
10
作者：
Hilliard, Tom N.;Regamey, Nicolas;Davies, Jane C.
通讯作者：
Davies, Jane C.
影响因子：
2.3
作者：
Katsumoto TR;Violette SM;Sheppard D
通讯作者：
Sheppard D
DOI：
10.1152/ajplung.00534.2007
发表时间：
2008-07-01
影响因子：
4.9
作者：
Ambalavanan, Namasivayam;Nicola, Teodora;Chen, Yiu-Fai
通讯作者：
Chen, Yiu-Fai
影响因子：
3.5
作者：
Bremer, Lindsay A.;Blackman, Scott M.;Cutting, Garry R.
通讯作者：
Cutting, Garry R.