The Role of Sphingolipid Signaling in Oxidative Lung Injury and Pathogenesis of Bronchopulmonary Dysplasia.
The Role of Sphingolipid Signaling in Oxidative Lung Injury and Pathogenesis of Bronchopulmonary Dysplasia.
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DOI：
10.3390/ijms23031254
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发表时间：
2022-01-23
影响因子：
5.6
通讯作者：
Harijith A
中科院分区：
文献类型：
--
作者：
Thomas JM;Sudhadevi T;Basa P;Ha AW;Natarajan V;Harijith A
早产儿出生时肺部发育迟缓，表面活性物质缺乏，缺乏抗氧化防御系统。由于涉及机械通风和氧气补充的护理方面的进步，这类婴儿的存活率显著提高。然而，这些幸存者中的一个重要亚群发展为慢性肺部疾病，即支气管肺发育不良(BPD)，其特征是肺泡扩大、简化和呼吸道变形。在许多致病因素中，高氧暴露于发育中的肺所引起的氧化损伤就是其中之一。最近的研究表明，高氧诱导神经鞘磷脂信号的异常，导致线粒体功能障碍和异常的活性氧(ROS)形成。神经酰胺和鞘氨醇1-磷酸(S1P)等鞘磷脂在BPD的发展中的作用是在过去十年中出现的。神经酰胺和S1P在发育为BPD的胎龄32周的早产儿的气管吸液中均升高。这一点在高氧和BPD的小鼠模型中得到了忠实的反映，在这些模型中，在肺组织和支气管肺泡灌洗中鞘磷脂代谢物的表达增加。用鞘氨醇激酶1特异性抑制剂PF543治疗新生幼鼠，结果是对新生儿BPD有保护作用，伴随着成年后肺功能的改善和呼吸道重塑的减少。伴随而来的是线粒体ROS形成减少。高氧诱导的S1P受体1也加重了BPD，揭示了BPD在此途径中的另一个潜在的药物靶点。在这篇综述中，我们旨在提供一个详细的描述神经鞘脂信号在高氧性肺损伤和BPD中所起的作用。
Premature infants are born with developing lungs burdened by surfactant deficiency and a dearth of antioxidant defense systems. Survival rate of such infants has significantly improved due to advances in care involving mechanical ventilation and oxygen supplementation. However, a significant subset of such survivors develops the chronic lung disease, Bronchopulmonary dysplasia (BPD), characterized by enlarged, simplified alveoli and deformed airways. Among a host of factors contributing to the pathogenesis is oxidative damage induced by exposure of the developing lungs to hyperoxia. Recent data indicate that hyperoxia induces aberrant sphingolipid signaling, leading to mitochondrial dysfunction and abnormal reactive oxygen species (ROS) formation (ROS). The role of sphingolipids such as ceramides and sphingosine 1-phosphate (S1P), in the development of BPD emerged in the last decade. Both ceramide and S1P are elevated in tracheal aspirates of premature infants of <32 weeks gestational age developing BPD. This was faithfully reflected in the murine models of hyperoxia and BPD, where there is an increased expression of sphingolipid metabolites both in lung tissue and bronchoalveolar lavage. Treatment of neonatal pups with a sphingosine kinase1 specific inhibitor, PF543, resulted in protection against BPD as neonates, accompanied by improved lung function and reduced airway remodeling as adults. This was accompanied by reduced mitochondrial ROS formation. S1P receptor1 induced by hyperoxia also aggravates BPD, revealing another potential druggable target in this pathway for BPD. In this review we aim to provide a detailed description on the role played by sphingolipid signaling in hyperoxia induced lung injury and BPD.
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影响因子：
5.1
作者：
Ambalavanan, Namasivayam;Cotten, C. Michael;Page, Grier P.;Carlo, Waldemar A.;Murray, Jeffrey C.;Bhattacharya, Soumyaroop;Mariani, Thomas J.;Cuna, Alain C.;Faye-Petersen, Ona M.;Kelly, David;Higgins, Rosemary D.
通讯作者：
Higgins, Rosemary D.
影响因子：
7.4
作者：
Berkelhamer, Sara K.;Kim, Gina A.;Radder, Josiah E.;Wedgwood, Stephen;Czech, Lyubov;Steinhorn, Robin H.;Schumacker, Paul T.
通讯作者：
Schumacker, Paul T.
DOI：
10.1158/1078-0432.ccr-16-2363
发表时间：
2017-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Britten CD;Garrett-Mayer E;Chin SH;Shirai K;Ogretmen B;Bentz TA;Brisendine A;Anderton K;Cusack SL;Maines LW;Zhuang Y;Smith CD;Thomas MB
通讯作者：
Thomas MB
影响因子：
62.1
作者：
Blaho, Victoria A.;Hla, Timothy
通讯作者：
Hla, Timothy
DOI：
10.1165/rcmb.2009-0174oc
发表时间：
2010-06-01
影响因子：
6.4
作者：
Becker, Katrin Anne;Riethmueller, Joachim;Gulbins, Erich
通讯作者：
Gulbins, Erich