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- Title
PPARγ activation in late gestation does not promote surfactant maturation in the fetal sheep lung.
- Authors
Ren, Jiaqi; Lock, Mitchell C.; Darby, Jack R. T.; Orgeig, Sandra; Holman, Stacey L.; Quinn, Megan; Seed, Mike; Muhlhausler, Beverly S.; McMillen, I. Caroline; Morrison, Janna L.
- Abstract
Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ; Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ, surfactant proteins (SFTP-A, -B, -C, and -D), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1. Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B. However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.
- Subjects
RESPIRATORY distress syndrome; PEROXISOME proliferator-activated receptors; PREMATURE infant death; SURFACE active agents; PHOSPHOLIPIDS
- Publication
Journal of Developmental Origins of Health & Disease, 2021, Vol 12, Issue 6, p963
- ISSN
2040-1744
- Publication type
Article
- DOI
10.1017/S204017442000135X