J 2019

Substrate mechanics controls adipogenesis through YAP phosphorylation by dictating cell spreading

OLIVER-DE, La Cruz Jorge, Giorgia NARDONE, Jan VRBSKY, Antonio POMPEIANO, Ana Rubina PERESTRELO et. al.

Základní údaje

Originální název

Substrate mechanics controls adipogenesis through YAP phosphorylation by dictating cell spreading

Autoři

OLIVER-DE, La Cruz Jorge, Giorgia NARDONE, Jan VRBSKY, Antonio POMPEIANO, Ana Rubina PERESTRELO, Francesco CAPRADOSSI, Katarina MELAJOVA, Petr FILIPENSKY a Giancarlo FORTE

Vydání

Biomaterials, OXFORD, ELSEVIER SCI LTD, 2019, 0142-9612

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30400 3.4 Medical biotechnology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 10.317

DOI

http://dx.doi.org/10.1016/j.biomaterials.2019.03.009

UT WoS

000464486600006

Klíčová slova anglicky

Cell-matrix interaction; Mechanobiology; Adipogenesis; Mesenchymal stem cells; Biocompatible hydrogels; Cell micropatterning; YAP; Mechanosensing

Štítky

CF GEN, ne MU

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 15. 10. 2024 09:03, Ing. Martina Blahová

Anotace

V originále

The mechanoregulated proteins YAP/TAZ are involved in the adipogenic/osteogenic switch of mesenchymal stem cells (MSCs). MSC fate decision can be unbalanced by controlling substrate mechanics, in turn altering the transmission of tension through cell cytoskeleton. MSCs have been proposed for orthopedic and reconstructive surgery applications. Thus, a tight control of their adipogenic potential is required in order to avoid their drifting towards fat tissue. Substrate mechanics has been shown to drive MSC commitment and to regulate YAP/TAZ protein shuttling and turnover. The mechanism by which YAP/TAZ co-transcriptional activity is mechanically regulated during MSC fate acquisition is still debated. Here, we design few bioengineering tools suited to disentangle the contribution of mechanical from biological stimuli to MSC adipogenesis. We demonstrate that the mechanical repression of YAP happens through its phosphorylation, is purely mediated by cell spreading downstream of substrate mechanics as dictated by dimensionality. YAP repression is sufficient to prompt MSC adipogenesis, regardless of a permissive biological environment, TEAD nuclear presence or focal adhesion stabilization. Finally, by harnessing the potential of YAP mechanical regulation, we propose a practical example of the exploitation of adipogenic transdifferentiation in tumors.
Zobrazeno: 31. 10. 2024 22:26