| Autor: |
Zhurenkov KE; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia.; Department of Cytology and Histology, St. Petersburg State University, St. Petersburg 199032, Russia., Lobov AA; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Bildyug NB; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Alexander-Sinclair EI; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Darvish DM; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Lomert EV; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Kriger DV; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Zainullina BR; Centre for Molecular and Cell Technologies, St. Petersburg State University, St. Petersburg 199032, Russia., Chabina AS; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Khorolskaya JI; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Perepletchikova DA; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Blinova MI; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia., Mikhailova NA; Institute of Cytology Russian Academy of Sciences, St. Petersburg 194064, Russia. |
| Abstrakt: |
The functioning of the human cornea heavily relies on the maintenance of its extracellular matrix (ECM) mechanical properties. Within this context, corneal stromal fibroblasts (CSFs) are essential, as they are responsible for remodeling the corneal ECM. In this study, we used a decellularized human amniotic membrane (dHAM) and a custom fibrillar collagen film (FCF) to explore the effects of fibrillar materials on human CSFs. Our findings indicate that substrates like FCF can enhance the early development of focal adhesions (FAs), leading to the activation and propagation of mechanotransduction signals. This is primarily achieved through FAK autophosphorylation and YAP1 nuclear translocation pathways. Remarkably, inhibiting FAK autophosphorylation negated the observed changes. Proteome analysis further confirmed the central role of FAs in mechanotransduction propagation in CSFs cultured on FCF. This analysis also highlighted complex signaling pathways, including chromatin epigenetic modifications, in response to fibrillar substrates. Overall, our research highlights the potential pathways through which CSFs undergo behavioral changes when exposed to fibrillar substrates, identifying FAs as essential mechanotransducers. |
