Abstract
Endothelial protein C receptor (EPCR) plays an important role in the protein C anticoagulation pathway and in the cytoprotective pathway. Previously, EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). Soluble EPCR levels are increased in patients with systemic inflammatory diseases. Recently, we reported that a new active compound, emodin-6-O-β-d-glucoside (EG) from Reynoutria japonica, has anti-inflammatory activities. However, little is known of the effects of EG on EPCR shedding. Here, we investigated this issue by monitoring the effects of EG on the phorbol-12-myristate 13-acetate (PMA) or the cecal ligation and puncture (CLP)-mediated EPCR shedding and its underlying mechanisms. Data showed that EG potently inhibited the PMA and CLP-induced EPCR shedding by suppressing TACE expression. Given these results, EG could be used as a candidate therapeutic for the treatment of vascular inflammatory diseases.
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Acknowledgments
This study was supported by the National Research Foundation of Korea (NRF) funded by the Korea government [MEST] (Grant No. 2012-0009400) and by the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. A111305).
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Wonhwa Lee and Sae-Kwang Ku contributed equally to this work.
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Lee, W., Ku, SK. & Bae, JS. Emodin-6-O-β-d-glucoside down-regulates endothelial protein C receptor shedding. Arch. Pharm. Res. 36, 1160–1165 (2013). https://doi.org/10.1007/s12272-013-0114-6
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DOI: https://doi.org/10.1007/s12272-013-0114-6