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

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) initia...

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Detalles Bibliográficos
Autores principales: Wasserman, Emily, Worgall, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Review
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688659/
https://www.ncbi.nlm.nih.gov/pubmed/34931265
http://dx.doi.org/10.1186/s40348-021-00130-y
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author Wasserman, Emily
Worgall, Stefan
author_facet Wasserman, Emily
Worgall, Stefan
author_sort Wasserman, Emily
collection PubMed
description 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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spelling pubmed-86886592022-01-05 Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma Wasserman, Emily Worgall, Stefan Mol Cell Pediatr Review 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. Springer Berlin Heidelberg 2021-12-20 /pmc/articles/PMC8688659/ /pubmed/34931265 http://dx.doi.org/10.1186/s40348-021-00130-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Wasserman, Emily
Worgall, Stefan
Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma
title Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma
title_full Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma
title_fullStr Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma
title_full_unstemmed Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma
title_short Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma
title_sort perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688659/
https://www.ncbi.nlm.nih.gov/pubmed/34931265
http://dx.doi.org/10.1186/s40348-021-00130-y
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