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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 SCXA, 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."},"dsDescriptionDate":{"typeName":"dsDescriptionDate","multiple":false,"typeClass":"primitive","value":"2020-01-20"}}]},{"typeName":"subject","multiple":true,"typeClass":"controlledVocabulary","value":["Medicine, Health and Life Sciences"]},{"typeName":"depositor","multiple":false,"typeClass":"primitive","value":"Hebels, Dennie"},{"typeName":"dateOfDeposit","multiple":false,"typeClass":"primitive","value":"2020-01-20"}]},"dansDataVaultMetadata":{"displayName":"Data Vault Metadata","name":"dansDataVaultMetadata","fields":[{"typeName":"dansDataversePid","multiple":false,"typeClass":"primitive","value":"doi:10.34894/VVATM8"},{"typeName":"dansDataversePidVersion","multiple":false,"typeClass":"primitive","value":"1.1"},{"typeName":"dansBagId","multiple":false,"typeClass":"primitive","value":"urn:uuid:d6e0bd22-5558-4997-a03c-7bffe3fa9b4b"},{"typeName":"dansNbn","multiple":false,"typeClass":"primitive","value":"urn:nbn:nl:ui:13-5a4f81b5-92a6-45aa-8f07-4e7991f66e04"}]}},"files":[{"description":"","label":"Mechanotransduction is a context-dependent activator of TGF-β signaling in mesenchymal stem cells.zip","restricted":false,"version":1,"datasetVersionId":30232,"dataFile":{"id":21009,"persistentId":"","filename":"Mechanotransduction is a context-dependent activator of TGF-β signaling in mesenchymal stem cells.zip","contentType":"application/zip","friendlyType":"ZIP Archive","filesize":1567311960,"description":"","storageIdentifier":"surf://store:16fc30271aa-088460a154ca","rootDataFileId":-1,"checksum":{"type":"SHA-1","value":"77ab0e1e7d45ce69dee8b5bb165f4ac7088a01ce"},"tabularData":false,"creationDate":"2020-01-20","publicationDate":"2020-08-18","lastUpdateTime":"2025-02-18T16:00:11Z","fileAccessRequest":false}}]}}}