View : 869 Download: 151
PAR-1 is a novel mechano-sensor transducing laminar flow-mediated endothelial signaling
- Title
- PAR-1 is a novel mechano-sensor transducing laminar flow-mediated endothelial signaling
- Authors
- Kim, Suji; Han, Jung-Hwa; Nam, Dae-Hwan; Kim, Geun-Young; Lim, Jae Hyang; Kim, Jae-Ryong; Woo, Chang-Hoon
- Ewha Authors
- 임재향
- SCOPUS Author ID
- 임재향
- Issue Date
- 2018
- Journal Title
- SCIENTIFIC REPORTS
- ISSN
- 2045-2322
- Citation
- SCIENTIFIC REPORTS vol. 8
- Publisher
- NATURE PUBLISHING GROUP
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Recent studies have indicated that protease-activated receptor-1 (PAR-1) is involved in cytoprotective and anti-inflammatory responses in endothelial cells (ECs). However, the role of PAR-1 in laminar flow-mediated atheroprotective responses remains unknown. Herein, we investigated whether PAR-1 regulates laminar flow-mediated mechanotransduction in ECs. Confocal analysis showed that PAR-1 was internalized into early endosomes in response to laminar flow. In addition, flow cytometry analysis showed that cell surface expression of PAR-1 was reduced by laminar flow, suggesting that PAR-1 was activated in response to laminar flow. Depletion of PAR-1 using human PAR-1 siRNA inhibited unidirectional laminar flow-mediated actin stress fiber formation and cellular alignment as well as atheroprotective gene expressions in HUVECs. Moreover, PAR-1 knockdown inhibited laminar flow-stimulated eNOS phosphorylation, and inhibited the phosphorylations of Src, AMPK, ERK5 and HDAC5. Furthermore, PAR-1 depletion inhibited laminar flow-mediated anti-inflammatory responses as demonstrated by reduced TNF alpha-induced VCAM-1 expression and by monocyte adhesion to HUVECs, and prevented laminar flow-mediated anti-apoptotic response. An investigation of the role of PAR-1 in vasomotor modulation using mouse aortic rings revealed that acetylcholine-induced vasorelaxation was diminished in PAR-1 deficient mice compared to littermate controls. Taken together, these findings suggest that PAR-1 be viewed as a novel pharmacologic target for the treatment of vascular diseases, including atherosclerosis.
- DOI
- 10.1038/s41598-018-33222-3
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
-
PAR-1 is a novel mechano-sensor.pdf(4.37 MB)
Download
- Export
- RIS (EndNote)
- XLS (Excel)
- XML