Title | Perinatal origins of chronic lung disease: mechanisms-prevention-therapy-sphingolipid metabolism and the genetic and perinatal origins of childhood asthma. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Wasserman E, Worgall S |
Journal | Mol Cell Pediatr |
Volume | 8 |
Issue | 1 |
Pagination | 22 |
Date Published | 2021 Dec 20 |
ISSN | 2194-7791 |
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. |
DOI | 10.1186/s40348-021-00130-y |
Custom 1 | |
Alternate Journal | Mol Cell Pediatr |
PubMed ID | 34931265 |
PubMed Central ID | PMC8688659 |
Grant List | KL2 TR002385 / TR / NCATS NIH HHS / United States R21 AI140724 / AI / NIAID NIH HHS / United States KL2 TR0002385 / TR / NCATS NIH HHS / United States |