Mechanotransduction is a context-dependent activator of TGF- β signaling in mesenchymal stem cells.

Mechanotransduction is a context-dependent activator of TGF-β signaling in mesenchymal stem cells. Biomaterials. 2020 Aug 15;259:120331 Authors: Vermeulen S, Roumans N, Honig F, Carlier A, Hebels DGAJ, Eren AD, Dijke PT, Vasilevich A, de Boer J Abstract We previously found that surface topographies induce the expression of the Scxa gene, encoding Scleraxis in tenocytes. Because Scxa is a TGF-β responsive gene, we investigated the link between mechanotransduction and TGF-β signaling. We discovered that mesenchymal stem cells exposed to both micro-topographies and TGF-β2 display synergistic induction of SMAD phosphorylation and transcription of the TGF-β target genes SCX, a-SMA, and SOX9. Pharmacological perturbations revealed that Rho/ROCK/SRF signaling is required for this synergistic response. We further found an activation of the early response genes SRF and EGR1 during the early adaptation phase on micro-topographies, which coincided with higher expression of the TGF-β type-II receptor gene. Of interest, PKC activators Prostratin and Ingenol-3, known for inducing actin reorganization and activation of serum response elements, were able to mimic the topography-induced TGF-β response. These findings provide novel insights into the convergence of mechanobiology and TGF-β signaling, which can lead to improved culture protocols and therapeutic applications. PMID: 32836056 [PubMed - as supplied by publisher]
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research