Please use this identifier to cite or link to this item:
|Title:||The CD47-binding peptide of thrombospondin-1 induces defenestration of liver sinusoidal endothelial cells|
Mechanical signal transduction
Myosin light chain
|Citation:||Venkatraman, L., Tucker-Kellogg, L. (2013-10). The CD47-binding peptide of thrombospondin-1 induces defenestration of liver sinusoidal endothelial cells. Liver International 33 (9) : 1386-1397. ScholarBank@NUS Repository. https://doi.org/10.1111/liv.12231|
|Abstract:||Background & Aims: A fenestrated phenotype is characteristic of liver sinusoidal endothelial cells (LSECs), but liver sinusoids become defenestrated during fibrosis and other liver diseases. Thrombospondin-1 (TSP1) is a matrix glycoprotein with pro-fibrotic effects, and the CD47-binding fragment of TSP1 also has anti-angiogenic effects in endothelial cells. We hypothesized that the CD47-binding fragment of TSP1 could induce defenestration in LSECs through the Rho-Rho kinase (ROCK)-myosin pathway. Methods: Freshly isolated rat LSECs were treated with TSP1 or CD47-binding peptides of TSP1. LSEC fenestration was assessed with scanning electron microscopy, and myosin phosphorylation was assessed with immuno-fluorescence. Results: Treating LSECs with TSP1 caused a dose-dependent loss of fenestrae, and this effect could not be blocked by SB-431542, the TGF-β1 receptor inhibitor. A CD47-binding fragment of TSP1, p4N1, was able to induce defenestration, and a CD47-blocking antibody, B6H12, was able to suppress p4N1-induced defenestration. The p4N1 fragment also caused contraction of fenestra size, correlated with an increase in myosin activation. Pretreatment with Y-237642 (a ROCK inhibitor) prevented p4N1-induced myosin activation and fenestrae decrease. Simvastatin has also been shown to antagonize Rho-ROCK signalling, and we found that simvastatin pretreatment protected LSECs from p4N1-induced myosin activation and defenestration. Conclusions: We conclude that CD47 signals through the Rho-ROCK-myosin pathway to induce defenestration in LSECs. In addition, our results show that simvastatin and Y-237642 have a beneficial impact on fenestration in vitro, providing an additional explanation for the efficacy of these compounds for regression of liver fibrosis. © 2013 The Authors. Liver International published by John Wiley & Sons Ltd.|
|Source Title:||Liver International|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Dec 3, 2018
WEB OF SCIENCETM
checked on Dec 3, 2018
checked on Nov 2, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.