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- W3016994911 abstract "Protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor functional expressed in several skin cell types including keratinocyte and dermal fibroblast. Thrombin-induced PAR1 activation play a crucial role in skin wound healing such as thrombosis, inflammation, proliferation and tissue repair. In the present study, we identified a novel positive allosteric modulator of PAR1, GB83, and investigated the effects of GB83 on skin wound healing. The enhancement of PAR1 activity by GB83 was measured using Fluo-4 calcium assay. Effects of GB83 on cell proliferation and gene expression were observed using MTS assay and quantitative real-time PCRs, respectively. SKH-1 hairless mice were used to investigate the wound healing effect of GB83. We demonstrated that GB83 did not activate PAR1 but strongly enhanced PAR1 activation by PAR1-AP and thrombin. GB83 significantly promoted PAR1-mediated cell proliferation and migration in HaCaT, HDF and A2058 cells. In addition, GB83 significantly increased gene expression of TGF-b, fibronectin and collagen type1, and promoted skin wound healing in the hairless mouse model. We have found that GB83, the first positive allosteric modulator of PAR1, significantly promotes skin wound healing in vitro and in vivo. These results suggest that GB83 may be a potential therapeutic reagent for skin wound healing." @default.
- W3016994911 created "2020-04-24" @default.
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- W3016994911 date "2020-04-01" @default.
- W3016994911 modified "2023-09-26" @default.
- W3016994911 title "Positive allosteric modulator of protease‐activated receptor 1 promotes skin wound healing in hairless mice" @default.
- W3016994911 doi "https://doi.org/10.1096/fasebj.2020.34.s1.05009" @default.
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