SP-A2 contributes to miRNA-mediated sex differences in response to oxidative stress

Pro-inflammatory, anti-apoptotic, and anti-oxidant pathways are involved

Georgios Noutsios, Nithyananda Thorenoor, Xuesheng Zhang, David S. Phelps, Todd M. Umstead, Faryal Durrani, Joanna Floros

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Human innate host defense molecules, surfactant protein A1 (SP-A1), and SP-A2 differentially affect the function and proteome of the alveolar macrophage (AM). We hypothesized that SP-A genes differentially regulate the AM miRNome. Methods: Humanized transgenic mice expressing SP-A1 and SP-A2 were subjected to O3-induced oxidative stress (OxS) or filtered air (FA), AMs were isolated, and miRNA levels were measured. Results: In SP-A2 males, we found significant changes in miRNome in terms of sex and sex-OxS effects, with 11 miRNAs differentially expressed under OxS. Their mRNA targets included BCL2, CAT, FOXO1, IL6, NF-kB, SOD2, and STAT3. We followed the expression of these transcripts as well as key cytokines, and we found that (a) the STAT3 mRNA significantly increased at 4 h post OxS and returned to baseline at 18 h post OxS. (b) The anti-oxidant protein SOD2 level significantly increased, but the CAT level did not change after 4 h post OxS compared to control. (c) The anti-apoptotic BCL2 mRNA increased significantly (18 h post OxS), but the levels of the other transcripts were decreased. The presence of the SP-A2 gene had a protective role in apoptosis of AMs under OxS compared to mice lacking SP-A (knockout, KO). (d) Pro-inflammatory cytokine IL-6 protein levels were significantly increased in SP-A2 mice compared to KO (4 and 18 h post OxS), which signifies the role of SP-A2 in pro-inflammatory protein expression. (e) SOD2 and CAT mRNAs changed significantly in OxS indicating a plausible role of SP-A2 in the homeostasis of reactive oxygen species. (f) Gonadectomy of transgenic mice showed that sex hormones contribute to significant changes of the miRNome expression. Conclusions: We conclude that SP-A2 influences the miRNA-mediated sex-specific differences in response to OxS. In males, these differences pertain to inflammatory, anti-apoptotic, and anti-oxidant pathways.

Original languageEnglish (US)
Article number37
JournalBiology of Sex Differences
Volume8
Issue number1
DOIs
StatePublished - Dec 4 2017
Externally publishedYes

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MicroRNAs
varespladib methyl
Oxidants
Sex Characteristics
Oxidative Stress
CAT
Messenger RNA
Alveolar Macrophages
Surface-Active Agents
Transgenic Mice
Interleukin-6
Proteins
vif Genes
Cytokines
NF-kappa B
Gonadal Steroid Hormones
Proteome
Reactive Oxygen Species
Homeostasis
Air

Keywords

  • IL-6
  • Ozone
  • Sex differences
  • STAT3
  • Surfactant protein A

ASJC Scopus subject areas

  • Gender Studies
  • Endocrinology

Cite this

SP-A2 contributes to miRNA-mediated sex differences in response to oxidative stress : Pro-inflammatory, anti-apoptotic, and anti-oxidant pathways are involved. / Noutsios, Georgios; Thorenoor, Nithyananda; Zhang, Xuesheng; Phelps, David S.; Umstead, Todd M.; Durrani, Faryal; Floros, Joanna.

In: Biology of Sex Differences, Vol. 8, No. 1, 37, 04.12.2017.

Research output: Contribution to journalArticle

Noutsios, Georgios ; Thorenoor, Nithyananda ; Zhang, Xuesheng ; Phelps, David S. ; Umstead, Todd M. ; Durrani, Faryal ; Floros, Joanna. / SP-A2 contributes to miRNA-mediated sex differences in response to oxidative stress : Pro-inflammatory, anti-apoptotic, and anti-oxidant pathways are involved. In: Biology of Sex Differences. 2017 ; Vol. 8, No. 1.
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AU - Zhang, Xuesheng

AU - Phelps, David S.

AU - Umstead, Todd M.

AU - Durrani, Faryal

AU - Floros, Joanna

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