Perinatal origins of chronic lung disease: mechanisms-prevention-therapy-sphingolipid metabolism and the genetic and perinatal origins of childhood asthma.

IF 2.4 Q1 PEDIATRICS

Molecular and cellular pediatrics Pub Date : 2021-12-20 DOI:10.1186/s40348-021-00130-y

Emily Wasserman, Stefan Worgall

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引用次数: 2

Abstract

Childhood asthma derives from complex host-environment interactions occurring in the perinatal and infant period, a critical time for lung development. Sphingolipids are bioactive molecules consistently implicated in the pathogenesis of childhood asthma. Genome wide association studies (GWAS) initially identified a link between alleles within the 17q21 asthma-susceptibility locus, childhood asthma, and overexpression of the ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), an inhibitor of de novo sphingolipid synthesis. Subsequent studies of pediatric asthma offer strong evidence that these asthma-risk alleles correlate with early-life aberrancies of sphingolipid homeostasis and asthma. Relationships between sphingolipid metabolism and asthma-related risk factors, including maternal obesity and respiratory viral infections, are currently under investigation. This review will summarize how these perinatal and early life exposures can synergize with 17q21 asthma risk alleles to exacerbate disruptions of sphingolipid homeostasis and drive asthma pathogenesis.

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慢性肺病的围产期起源:机制-预防-治疗-鞘脂代谢以及儿童哮喘的遗传和围产期起源。

儿童哮喘源于围产期和婴儿期发生的复杂的宿主-环境相互作用，这是肺部发育的关键时期。鞘脂是一种生物活性分子，一直与儿童哮喘的发病机制有关。基因组全关联研究(GWAS)最初发现了17q21哮喘易感位点、儿童哮喘和ORMDL鞘脂生物合成调节因子3 (ORMDL3)过表达之间的联系，ORMDL3是一种新生鞘脂合成抑制剂。随后对儿童哮喘的研究提供了强有力的证据，表明这些哮喘风险等位基因与生命早期神经鞘脂稳态异常和哮喘相关。鞘脂代谢与哮喘相关危险因素(包括产妇肥胖和呼吸道病毒感染)之间的关系目前正在调查中。本文将总结这些围产期和生命早期暴露如何与17q21哮喘风险等位基因协同作用，加剧鞘脂稳态的破坏并驱动哮喘发病机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular and cellular pediatrics

CiteScore

2.20

自引率

0.00%

发文量