Modulatory Effects of Dabigatran on PAR-1 Activity and Viability in Adipose-Derived Mesenchymal Stem Cells
International Journal of Molecular Sciences, vol.27, no.9, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 27 Issue: 9
- Publication Date: 2026
- Doi Number: 10.3390/ijms27093783
- Journal Name: International Journal of Molecular Sciences
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
- Keywords: ADMSs, cell viability, dabigatran, NOACs, PAR-1 signaling
- Hacettepe University Affiliated: Yes
Abstract
Protease-activated receptor-1 (PAR-1) is a key regulator of mesenchymal stem cell (MSC) migration and tissue integration. Dabigatran, a direct thrombin inhibitor widely used as a non-vitamin K oral anticoagulant (NOAC), may affect PAR-1-mediated signaling pathways. This study investigated the effects of dabigatran on cell viability, apoptosis, and PAR-1 activity in adipose-derived MSCs (ADMSCs) in vitro. ADMSCs were exposed to five concentrations of dabigatran etexilate with thrombin activation. Cell viability was assessed using the MTT assay, apoptosis and morphological changes were evaluated via acridine orange/propidium iodide staining, and PAR-1 expression was analyzed by immunofluorescence. Results showed that high dabigatran concentration significantly reduced cell viability and induced apoptotic morphological changes. In contrast, lower, non-cytotoxic concentrations preserved normal fibroblastic morphology and maintained cell viability while reducing PAR-1 surface expression compared with thrombin-activated controls. These findings indicate that dabigatran at non-cytotoxic doses can modulate PAR-1 activity without compromising ADMSC survival. In conclusion, dabigatran influences MSC-related cellular functions beyond its anticoagulant properties.