Differential Sex-Dependent Regulation of the Alveolar Macrophage miRNome of SP-A2 and co-ex (SP-A1/SP-A2) and Sex Differences Attenuation after 18 h of Ozone Exposure

• Main Authors: Nithyananda Thorenoor (Author), David S. Phelps (Author), Joanna Floros (Author)
• Format: Book
• Published: MDPI AG, 2020-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox9121190; 2076-3921
• Keywords: alveolar macrophages; miRNA; SP-A2; co-ex (SP-A1/SP-A2); surfactant; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 9, Iss 12, p 1190 (2020)

Background: Human SP-A1 and SP-A2, encoded by <i>SFTPA1</i> and <i>SFTPA2</i>, 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 (O₃)_. AM miRNA levels, target gene expression, and pathways determined 18 h after O₃ 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 O₃, 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) O₃ exposure attenuated sex differences with a higher number of genotype-dependent and genotype-independent miRNAs common in both sexes after O₃ exposure. Conclusion: Qualitative differences between SP-A2 and co-ex persist 18 h post-O₃, and O₃ attenuates sex differences.