SP-A2 contributes to miRNA-mediated sex differences in response to oxidative stress: pro-inflammatory, anti-apoptotic, and anti-oxidant pathways are involved.

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 s

SUBMITTER: Noutsios GT 

PROVIDER: S-EPMC5716385 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature