Gene expression changes reveal the impact of the space environment on the skin of International Space Station astronauts

Abstract

Background: The various types of ionizing radiation and altered gravity in the space environment present a risk to humans during space missions. Changes in the space environment lead to skin diseases, affecting the status of the aviators to fly. Therefore, it is important to explore the molecular-level changes in the skin during space missions.

Objectives: Bioinformatics analysis of gene arrays from hair follicle tissue of 10 astronauts was performed to explore changes in gene expression before, during and after space missions.

Methods: First, STEM (Short Time-series Expression Miner) software was used to identify the expression patterns of hair follicle genes of astronauts pre-, in- and postflight. Gene Ontology Enrichment Analysis was then performed to explore the gene functions within the module. Protein-protein interaction network analysis was performed on skin-related genes. The transcriptional regulatory network within the module was constructed using the TRRUST database. The circadian rhythm-related genes within the module were screened using the MSigDB (Molecular Signatures Database).

Results: Based on differential expression analysis between the two groups, there were 327 differentially expressed genes after the astronauts entered space compared with preflight, and only 54 differentially expressed genes after returning to Earth. This outcome suggests that the expression of most genes can be recovered on return to the ground, but there are a small number of genes whose expression cannot be recovered in a short period of time. Based on time series analysis, 311 genes showed increased expression on entry into space and decreased expression on return to Earth. The genes of this expression pattern were associated with skin development, keratinocyte differentiation and cornification. Ten hub genes were identified as skin-related genes within the module, as well as nine transcription factors and three circadian genes. One hundred and seventy-nine genes decreased in expression after entry into space and increased on return to Earth. By reviewing the literature, we found that four of the genes, CSCD2, HP, CXCR1 and SSTR4, are associated with skin diseases.

Conclusions: Through bioinformatics analysis, we found that the space environment affects skin keratinocyte differentiation, leading to skin barrier damage and inflammatory responses, and that this effect was decreased after return to Earth.