Simulated microgravity triggers epithelial mesenchymal transition in human keratinocytes

Abstract

The microgravitational environment is known to affect the cellular behaviour inducing modulation of gene expression and enzymatic activities, epigenetic modifications and alterations of the structural organization. Simulated microgravity, obtained in the laboratory setting through the use of a Random Positioning Machine (RPM), represents a well recognized and useful tool for the experimental studies of the cellular adaptations and molecular changes in response to weightlessness. Short exposure of cultured human keratinocytes to the RPM microgravity influences the cellular circadian clock oscillation. Therefore, here we searched for changes on the regenerative ability and response to tissue damage of human epidermal cells through the analysis of the effects of the simulated microgravity on the re-epithelialization phase of the repair and wound healing process. Combining morphological, biochemical and molecular approaches, we found that the simulated microgravity exposure of human keratinocytes promotes a migratory behavior and triggers the epithelial-mesenchymal transition (EMT) through expression of the typical EMT transcription factors and markers, such as Snail1, Snail2 and ZEB2, metalloproteases, mesenchymal adhesion molecules and cytoskeletal components.

Effectiveness of endothelial progenitor cell culture under microgravity for improved angiogenic potential

“…While MMP-2 levels increased, MMP-9 levels decreased. The decreases in MMP-9 levels that we observed is in contrast to previous studies 29 , and it is likely that the differences in these results could be due to differences in the experimental setups or differences in the cell types that were studied.…”

Changes in Nuclear Shape and Gene Expression in Response to Simulated Microgravity Are LINC Complex-Dependent

“…For decades, cells have been studied in altered gravity environments using various platforms such as the International Space Station, sounding rockets, parabolic flights and microgravity simulators. Common cell functions such as proliferation, migration, division and differentiation are all affected differently in altered gravity environments [ 13 , 36 , 54 , 55 ]. Genes associated with the progression of cancer by metastasis (cytokines) are also differentially regulated in microgravity as are several other genes related to wound healing, focal adhesion [ 13 ], and growth factors.…”

Gravity Constraints Drive Biological Systems Toward Specific Organization Patterns

“…Even very “weak” forces, such as those displayed by electromagnetic and gravitational fields, can be “amplified” when the system encounters a bifurcation point from which it is driven in undergoing a “phase transition,” leading to different attractor states . In fact, we have already demonstrated that microgravity is able to trigger a complex, concerted array of changes leading to the epithelial‐mesenchymal transition in living cells …”