Docosatetraenoyl LPA is elevated in exhaled breath condensate in idiopathic pulmonary fibrosis.
Docosatetraenoyl LPA is elevated in exhaled breath condensate in idiopathic pulmonary fibrosis.
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DOI：
10.1186/1471-2466-14-5
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发表时间：
2014-01-27
影响因子：
3.1
通讯作者：
Shea BS
中科院分区：
文献类型：
--
作者：
Montesi SB;Mathai SK;Brenner LN;Gorshkova IA;Berdyshev EV;Tager AM;Shea BS
特发性肺纤维化（IPF）是一种进行性、致命性的疾病，没有有效的药物治疗方法。最近的研究重点是确定纤维化发生和进展所必需的生物过程，以及驱动这些过程的介质。溶血磷脂酸 (LPA) 是一种具有生物活性的溶血磷脂，就是这样的介质之一。研究发现，IPF 患者的支气管肺泡灌洗 (BAL) 液中 LPA 升高，并且通过与其细胞表面受体相互作用，LPA 已被证明可驱动与 IPF 发展有关的多种生物过程。因此，LPA 受体拮抗剂治疗 IPF 的首个临床试验最近已启动。除了作为治疗靶点外，LPA 还具有成为 IPF 生物标志物的潜力。人们对呼出气冷凝物 (EBC) 分析作为肺部疾病生物标志物检测的非侵入性方法越来越感兴趣，但 EBC 中 LPA 的存在程度尚不清楚。在这项研究中，我们使用液相色谱-串联质谱 (LC-MS/MS) 来评估 11 名 IPF 受试者和 11 名对照者的 EBC 和血浆中是否存在 LPA。在 EBC 中总共检测到 9 种不同的 LPA 种类。其中，与对照组相比，IPF 受试者 EBC 中的二十二碳四烯酰 (22:4) LPA 显着升高（9.18 pM vs. 0.34 pM；p = 0.001）。血浆中总共可检测到 13 种不同的 LPA 种类，但与 EBC 相比，IPF 受试者和对照组之间的血浆 LPA 种类没有统计学上的显着差异。这些结果表明，在 EBC 中可检测到多种 LPA，并且 IPF 患者的 EBC 中 22:4 LPA 水平升高。需要进一步的研究来确定 22:4 LPA 在 IPF EBC 中升高的意义，以及其作为疾病严重程度和/或进展的生物标志物的潜力。
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective medical therapies. Recent research has focused on identifying the biological processes essential to the development and progression of fibrosis, and on the mediators driving these processes. Lysophosphatidic acid (LPA), a biologically active lysophospholipid, is one such mediator. LPA has been found to be elevated in bronchoalveolar lavage (BAL) fluid of IPF patients, and through interaction with its cell surface receptors, it has been shown to drive multiple biological processes implicated in the development of IPF. Accordingly, the first clinical trial of an LPA receptor antagonist in IPF has recently been initiated. In addition to being a therapeutic target, LPA also has potential to be a biomarker for IPF. There is increasing interest in exhaled breath condensate (EBC) analysis as a non-invasive method for biomarker detection in lung diseases, but to what extent LPA is present in EBC is not known. In this study, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess for the presence of LPA in the EBC and plasma from 11 IPF subjects and 11 controls. A total of 9 different LPA species were detectable in EBC. Of these, docosatetraenoyl (22:4) LPA was significantly elevated in the EBC of IPF subjects when compared to controls (9.18 pM vs. 0.34 pM; p = 0.001). A total of 13 different LPA species were detectable in the plasma, but in contrast to the EBC, there were no statistically significant differences in plasma LPA species between IPF subjects and controls. These results demonstrate that multiple LPA species are detectable in EBC, and that 22:4 LPA levels are elevated in the EBC of IPF patients. Further research is needed to determine the significance of this elevation of 22:4 LPA in IPF EBC, as well as its potential to serve as a biomarker for disease severity and/or progression.
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影响因子：
3.5
作者：
Bandoh, K;Aoki, J;Inoue, K
通讯作者：
Inoue, K
影响因子：
--
作者：
Antczak, Adam;Piotrowski, Wojciech;Barnes, Peter J.
通讯作者：
Barnes, Peter J.
DOI：
10.1165/rcmb.2013-0070oc
发表时间：
2013-12-01
影响因子：
6.4
作者：
Huang, Long Shuang;Fu, Panfeng;Natarajan, Viswanathan
通讯作者：
Natarajan, Viswanathan
影响因子：
14.2
作者：
Kazani, Shamsah;Planaguma, Anna;Israel, Elliot
通讯作者：
Israel, Elliot
在硬皮病小鼠模型中通过基因缺失或溶血磷脂酸受体 1 的药理学拮抗作用改善真皮纤维化。
影响因子：
--
作者：
Castelino, Flavia V.;Seiders, Jon;Bain, Gretchen;Brooks, Sarah F.;King, Christopher D.;Swaney, James S.;Lorrain, Daniel S.;Chun, Jerold;Luster, Andrew D.;Tager, Andrew M.
通讯作者：
Tager, Andrew M.