ORMDL3 与过敏性哮喘：从生理学到病理学。
ORMDL3 and allergic asthma: From physiology to pathology.
机构信息
Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Va.
Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Va.
出版信息
J Allergy Clin Immunol. 2019 Sep;144(3):634-640. doi: 10.1016/j.jaci.2019.07.023. Epub 2019 Jul 31.
Abstract
There is a strong genetic component to asthma, and numerous genome-wide association studies have identified ORM1 (yeast)-like protein 3 (ORMDL3) as a gene associated with asthma susceptibility. However, how ORMDL3 contributes to asthma pathogenesis and its physiologic functions is not well understood and a matter of great debate. This rostrum describes recent advances and new insights in understanding of the multifaceted functions of ORMDL3 in patients with allergic asthma. We also suggest a potential unifying paradigm and discuss molecular mechanisms for the pathologic functions of ORMDL3 in asthma related to its evolutionarily conserved role in regulation of sphingolipid homeostasis. Finally, we briefly survey the utility of sphingolipid metabolites as potential biomarkers for allergic asthma.
摘要
哮喘有很强的遗传因素，许多全基因组关联研究已经确定 ORM1（酵母）样蛋白 3（ORMDL3）是与哮喘易感性相关的基因。然而，ORMDL3 如何导致哮喘发病机制及其生理功能尚不清楚，这是一个争论的焦点。本专题描述了在理解变应性哮喘患者 ORMDL3 的多方面功能方面的最新进展和新见解。我们还提出了一个潜在的统一范式，并讨论了 ORMDL3 在哮喘中的病理功能的分子机制，这与其在调节鞘脂类稳态方面的进化保守作用有关。最后，我们简要调查了鞘脂代谢物作为潜在的变应性哮喘生物标志物的用途。
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本文引用的文献
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The ORMDL/Orm-serine palmitoyltransferase (SPT) complex is directly regulated by ceramide: Reconstitution of SPT regulation in isolated membranes.ORMDL/Orm 丝氨酸棕榈酰转移酶（SPT）复合物受神经酰胺直接调节：在分离的膜中重建 SPT 调节。
J Biol Chem. 2019 Mar 29;294(13):5146-5156. doi: 10.1074/jbc.RA118.007291. Epub 2019 Jan 30.
2
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Myristate-induced endoplasmic reticulum stress requires ceramide synthases 5/6 and generation of C14-ceramide in intestinal epithelial cells.豆蔻酸诱导的内质网应激需要肠道上皮细胞中的神经酰胺合酶 5/6 和 C14-神经酰胺的生成。
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Role of local CpG DNA methylation in mediating the 17q21 asthma susceptibility gasdermin B (GSDMB)/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) expression quantitative trait locus.局部CpG DNA甲基化在介导17q21哮喘易感性gasdermin B（GSDMB）/鞘脂生物合成调节因子3（ORMDL3）表达数量性状位点中的作用。
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