Inhibition of TGF-β signaling and decreased apoptosis in IUGR-associated lung disease in rats.
Inhibition of TGF-β signaling and decreased apoptosis in IUGR-associated lung disease in rats.
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DOI：
10.1371/journal.pone.0026371
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Dötsch J
中科院分区：
文献类型：
--
作者：
Alejandre Alcázar MA;Morty RE;Lendzian L;Vohlen C;Oestreicher I;Plank C;Schneider H;Dötsch J
胎儿宫内发育受限与成年期肺功能受损有关。目前尚不清楚这种肺功能损害是否与肺内转化生长因子-β系统有关。因此，我们研究了宫内发育迟缓对大鼠肺功能、细胞外基质成分表达和转化生长因子-β信号转导的影响。用等热量蛋白限制孕期诱导大鼠宫内发育迟缓。在出生后第70天用直接体积描记法评估肺功能。于术后第1天和第70天测定肺组织转化生长因子-β系统的肺活性。体外用腺病毒介导的Smad7阻断转化生长因子-β信号转导。在P70，IUGR后呼吸道顺应性明显受损。伴随这些变化的是，转化生长因子-Smad1在P1和P70的表达减少，以及Smad2和Smad3的磷酸化持续抑制。此外，宫内发育迟缓组大鼠肺组织中转化生长因子-β信号转导抑制物(Smad7和S-β)的表达水平降低，I型胶原等细胞外基质成分的表达减少，弹性蛋白和张力蛋白N的表达显著上调。在体外，腺病毒介导的Smad7对NIH/3T3、MLE12和内皮细胞转化生长因子-β信号的抑制作用直接影响细胞外基质成分的表达。综上所述，这些数据显示了宫内发育迟缓对肺发育和功能的显著影响，并提示转化生长因子-β信号减弱可能参与宫内发育迟缓相关肺部疾病的病理过程。
Intrauterine growth restriction is associated with impaired lung function in adulthood. It is unknown whether such impairment of lung function is linked to the transforming growth factor (TGF)-β system in the lung. Therefore, we investigated the effects of IUGR on lung function, expression of extracellular matrix (ECM) components and TGF-β signaling in rats. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 70. Pulmonary activity of the TGF-β system was determined at P1 and P70. TGF-β signaling was blocked in vitro using adenovirus-delivered Smad7. At P70, respiratory airway compliance was significantly impaired after IUGR. These changes were accompanied by decreased expression of TGF-β1 at P1 and P70 and a consistently dampened phosphorylation of Smad2 and Smad3. Furthermore, the mRNA expression levels of inhibitors of TGF-β signaling (Smad7 and Smurf2) were reduced, and the expression of TGF-β-regulated ECM components (e.g. collagen I) was decreased in the lungs of IUGR animals at P1; whereas elastin and tenascin N expression was significantly upregulated. In vitro inhibition of TGF-β signaling in NIH/3T3, MLE 12 and endothelial cells by adenovirus-delivered Smad7 demonstrated a direct effect on the expression of ECM components. Taken together, these data demonstrate a significant impact of IUGR on lung development and function and suggest that attenuated TGF-β signaling may contribute to the pathological processes of IUGR-associated lung disease.
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DOI：
10.1152/ajplung.00050.2006
发表时间：
2007-02-01
影响因子：
4.9
作者：
Alejandre-Alcazar, Miguel A.;Kwapiszewska, Grazyna;Morty, Rory E.
通讯作者：
Morty, Rory E.
DOI：
10.1152/ajplung.00298.2004
发表时间：
2005-04-01
影响因子：
4.9
作者：
Chen, H;Sun, JP;Shi, W
通讯作者：
Shi, W
影响因子：
3.6
作者：
Hosford, GE;Fang, X;Olson, DM
通讯作者：
Olson, DM
影响因子：
3.6
作者：
Dik, WA;De Krijger, RR;Versnel, MA
通讯作者：
Versnel, MA
影响因子：
13.5
作者：
Freathy, C;Brown, DG;Cain, K
通讯作者：
Cain, K