Journal
ANTIOXIDANTS
Volume 9, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/antiox9121190
Keywords
alveolar macrophages; miRNA; SP-A2; co-ex (SP-A1; SP-A2); surfactant
Funding
- CHILD fund, Department of Pediatrics, College of Medicine at Pennsylvania State University
- John Ardell Pursley Memorial Research Fund
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Background: Human SP-A1 and SP-A2, encoded by SFTPA1 and SFTPA2, and their genetic variants differentially impact alveolar macrophage (AM) functions and regulation, including the miRNome. We investigated whether miRNome differences previously observed between AM from SP-A2 and SP-A1/SP-A2 mice are due to continued qualitative differences or a delayed response of mice carrying a single gene. Methods: Human transgenic (hTG) mice, carrying SP-A2 or both SP-A genes, and SP-A-KO mice were exposed to filtered air (FA) or ozone (O-3)(.) AM miRNA levels, target gene expression, and pathways determined 18 h after O-3 exposure. RESULTS: We found (a) differences in miRNome due to sex, SP-A genotype, and exposure; (b) miRNome of both sexes was largely downregulated by O-3, and co-ex had fewer changed (>= 2-fold) miRNAs than either group; (c) the number and direction of the expression of genes with significant changes in males and females in co-ex are almost the opposite of those in SP-A2; (d) the same pathways were found in the studied groups; and (e) O-3 exposure attenuated sex differences with a higher number of genotype-dependent and genotype-independent miRNAs common in both sexes after O-3 exposure. Conclusion: Qualitative differences between SP-A2 and co-ex persist 18 h post-O-3, and O-3 attenuates sex differences.
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