Dataset Information

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.

ABSTRACT:

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 (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.

SUBMITTER: Thorenoor N

PROVIDER: S-EPMC7768498 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

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.

Thorenoor Nithyananda N Phelps David S DS Floros Joanna J

Antioxidants (Basel, Switzerland) 20201127 12

<h4>Background</h4>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.<h4>Methods</h4>Human transgenic (hTG) mice, carrying SP-A2 or both SP-A genes, and SP ...[more]

PMID: 33260937

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Project description:Surfactant protein A (SP-A) plays critical roles in host defense, regulation of inflammation and surfactant metabolism in the lung. The human SP-A locus consists of two functional genes, SFTPA1 and SFTPA2 encoding surfactant proteins SP-A1 and SP-A2, respectively. Structural and functional differences exist between SP-A1 and SP-A2 in vitro and in vivo. Ozone is a major air pollutant with a negative impact on many biological processes. In this study we used humanized transgenic (hTG) SP-A1 and SP-A2 mice, and SP-A KO mice to study in vivo effects of SP-A1 and SP-A2 on the bronchoalveolar lavage (BAL) proteomic profile and associated signaling pathways in response to ozone or filtered air (FA) exposure and Klebsiella pneumoniae infection. The BAL samples were harvested 24 h after ozone (2 ppm for 3 h) or FA exposure and infection and analyzed by two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-ToF/ToF. We found: that (1) Ozone exposure, but not infection, is a major factor for increases in total BAL protein content. (2) A total of 36 proteins were identified, accounting for 89.62% of the BAL proteins resolved by the 2D-DIGE system. (3) The number of proteins in which levels were altered more than 25% following infection and FA exposure was: SP-A2 > SP-A1 > KO for male mice, and SP-A2 ≈ SP-A1 > KO for female mice. (4) The number of proteins with more than 25% increase/decrease after ozone exposure and infection was: SP-A2 > SP-A1 ≈ KO, with the majority being increases in male mice and decreases in female mice. (5) Eleven out of the 36 proteins, including annexin A5, glutathione S-transferase A4, SP-A1/SP-A2, and 14-3-3 zeta protein, exhibited significant differences among SP-A genotypes. The acute phase response (APR) that includes the NF-kB signaling pathway plays a critical role, followed by Nrf2-mediated oxidative response, and others. These associated with SP-A genotype, sex, and ozone-induced oxidative stress in response to infection. We concluded that human SP-A2 and SP-A1 exhibit differential genotype-and sex-dependent innate immune responses to microbial pathogens and/or ozone-induced oxidative stress by modulating proteomic patterns and signaling pathways in the lung.

Dataset Information

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.

Background

Methods

Results

Conclusion

Publications

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.

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