Keywords

galactic cosmic radiation; solar particle event; microgravity; hepatology; fibrosis; senescence

Abstract

With the start of NASA’s Artemis program, astronauts will soon leave the protection of Earth’s magnetosphere. Previous studies have established a theme of liver dysregulation associated with the harmful radiation and microgravity experienced in deep space. MicroRNAs (miRNAs) are key regulators of many of the pathologies observed during and after spaceflight, including hepatic fibrosis, making them strong potential biomarkers and therapeutic targets. Therefore, in the present study we investigated the effects of simulated microgravity, galactic cosmic radiation (GCR), and solar particle events (SPE) on miRNAs and mRNAs involved in the TGF-β signaling pathway, a key regulator of fibrosis, senescence, and inflammation in the liver. We also analyzed the ability of an antagomir treatment which targets miR-16-5p, miR-125b-5p, and let-7a-5p to modulate these spaceflight-associated changes in liver health. Our results indicate that the observed miRNA profile widely varied depending on whether GCR or SPE irradiation were administered. Likewise, while the antagomir treatment was successful at downregulating expression of its target mRNAs, the type of radiation received greatly influenced whether the miRNA shifts observed correlated with changes in downstream gene expression; the GCR group was the most effected and the SPE the least in terms of both miRNA and mRNA expression. Overall, the current study highlights the profound effects of cosmic radiation on the hepatic miRNA profile and confirms the potential of antagomir treatment as a therapeutic for spaceflight induced changes in expression.

Thesis Completion Year

2024

Thesis Completion Semester

Spring

Thesis Chair

Masternak, Michal

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Biomedical Sciences

Language

English

Access Status

Open Access

Length of Campus Access

None

Campus Location

Orlando (Main) Campus

Download

Share

COinS