Reactive oxygen species as signaling molecules in the development of lung fibrosis.
Reactive oxygen species as signaling molecules in the development of lung fibrosis.
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DOI：
10.1016/j.trsl.2017.09.005
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Budinger GRS
中科院分区：
文献类型：
--
作者：
Gonzalez-Gonzalez FJ;Chandel NS;Jain M;Budinger GRS
肺纤维化是一种相对罕见但具有破坏性的疾病，其特征是细胞外基质过度沉积。基质增加导致肺顺应性降低和呼吸功增加，肺泡-毛细血管结构闭塞可导致低氧血症和肺动脉高压，临床表现为呼吸短促加重、呼吸衰竭和死亡。无偏倚全基因组关联研究结合动物模型表明肺泡上皮损伤是肺纤维化的起始因素。这种上皮损伤导致肌成纤维细胞的激活和增殖，这些细胞分泌纤维化特征的细胞外基质蛋白。在肺泡上皮功能障碍与肌成纤维细胞活化和增殖之间的分子联系中，被描述得最好的是促纤维化细胞因子转化生长因子-β (TGF-β)。我们和其他人发现线粒体和NADPH氧化酶产生的活性氧（ROS）发挥信号传导作用，增强TGF-β信号传导，促进纤维化。本综述的目的是对TGF-β激活下游的ROS信号进行综述。我们认为，对这些途径的更好理解可能解释了非选择性抗氧化剂在改善肺纤维化患者预后方面的失败，并可能确定新的治疗靶点。
Pulmonary fibrosis is a relatively rare but devastating disease characterized by the excessive deposition of extracellular matrix. The increased matrix results in reduced lung compliance and increased work of breathing, while the obliteration of alveolar-capillary structures can result in hypoxemia and pulmonary hypertension, which manifests clinically as worsening shortness of breath, respiratory failure and death. Unbiased genome wide association studies combined with animal models suggest that damage to the alveolar epithelium is the initiating factor in pulmonary fibrosis. This epithelial injury leads to the activation and proliferation of myofibroblasts that secrete extracellular matrix proteins characteristic of fibrosis. The best described molecular link between alveolar epithelial dysfunction and myofibroblast activation and proliferation is the profibrotic cytokine transforming growth factor-β (TGF-β). We and others have found that mitochondrial and NADPH oxidase-generated reactive oxygen species (ROS) play a signaling role to enhance TGF-β signaling and promote fibrosis. This purpose of this review is to review ROS signaling downstream of the activation of TGF-β. We suggest that an improved understanding of these pathways might explain the failure of nonselective antioxidants to improve outcomes in patients with pulmonary fibrosis and might identify novel targets for therapy.
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DOI：
10.1146/annurev-pathol-020712-163930
发表时间：
2013-01-24
期刊：
Annual review of pathology
影响因子：
--
作者：
Duffield JS;Lupher M;Thannickal VJ;Wynn TA
通讯作者：
Wynn TA
DOI：
10.1056/nejmoa1216076
发表时间：
2013-06-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hunninghake GM;Hatabu H;Okajima Y;Gao W;Dupuis J;Latourelle JC;Nishino M;Araki T;Zazueta OE;Kurugol S;Ross JC;San José Estépar R;Murphy E;Steele MP;Loyd JE;Schwarz MI;Fingerlin TE;Rosas IO;Washko GR;O'Connor GT;Schwartz DA
通讯作者：
Schwartz DA
影响因子：
4.8
作者：
Jain, Manu;Rivera, Stephanie;Chandel, Navdeep S.
通讯作者：
Chandel, Navdeep S.
DOI：
10.1165/rcmb.2013-0519oc
发表时间：
2015-01-01
影响因子：
6.4
作者：
Jaffer, Omar A.;Carter, A. Brent;Anderson, Mark E.
通讯作者：
Anderson, Mark E.
DOI：
10.1097/01.asn.0000077411.98742.54
发表时间：
2003-08-01
影响因子：
13.6
作者：
Ha, H;Lee, HB
通讯作者：
Lee, HB