Microgravity Induces Transient EMT in Human Keratinocytes by Early Down-Regulation of E-Cadherin and Cell-Adhesion Remodeling

Applied Sciences

Marcella Cammarota¹  Francesca Ferranti²  Mariano Bizzarri³  Giulia Ricci⁴  Antonio Filippini⁴  Angela Catizone⁵  Alessandra Cucina⁵  Sara Proietti⁵  Simona Dinicola⁵ 

[1] Via del Politecnico s.n.c. 00133 Roma, Italy;ASI Agenzia Spaziale Italiana;Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Section of Histology and Embryology, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy;Department of Experimental Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy;Systems Biology Group Laboratory, Sapienza University, 00161 Rome, Italy;

关键词: simulated microgravity;    focal adhesion;    vinculin;    E-cadherin;    cytoskeleton;    HaCaT cells;   

DOI  :  10.3390/app11010110

来源: DOAJ

【 摘 要 】

Changes in cell–matrix and cell-to-cell adhesion patterns are dramatically fostered by the microgravity exposure of living cells. The modification of adhesion properties could promote the emergence of a migrating and invasive phenotype. We previously demonstrated that short exposure to the simulated microgravity of human keratinocytes (HaCaT) promotes an early epithelial–mesenchymal transition (EMT). Herein, we developed this investigation to verify if the cells maintain the acquired invasive phenotype after an extended period of weightlessness exposure. We also evaluated cells’ capability in recovering epithelial characteristics when seeded again into a normal gravitational field after short microgravity exposure. We evaluated the ultra-structural junctional features of HaCaT cells by Transmission Electron Microscopy and the distribution pattern of vinculin and E-cadherin by confocal microscopy, observing a rearrangement in cell–cell and cell–matrix interactions. These results are mirrored by data provided by migration and invasion biological assay. Overall, our studies demonstrate that after extended periods of microgravity, HaCaT cells recover an epithelial phenotype by re-establishing E-cadherin-based junctions and cytoskeleton remodeling, both being instrumental in promoting a mesenchymal–epithelial transition (MET). Those findings suggest that cytoskeletal changes noticed during the first weightlessness period have a transitory character, given that they are later reversed and followed by adaptive modifications through which cells miss the acquired mesenchymal phenotype.

【 授权许可】

Unknown