fulltext.study @t Gmail

The role of endothelial cell-bound Jagged1 in Notch3-induced human coronary artery smooth muscle cell differentiation

Paper ID Volume ID Publish Year Pages File Format Full-Text
6989 527 2012 11 PDF Available
Title
The role of endothelial cell-bound Jagged1 in Notch3-induced human coronary artery smooth muscle cell differentiation
Abstract

Phenotype regulation of vascular smooth muscle cells (VSMC) is an important requirement in both tissue engineering and balloon angioplasty strategies. In recent years, it has become increasingly evident that the Notch signalling pathway plays a critical role in regulating vascular morphogenesis during development and the transcription of differentiated VSMC and its maturation. In arteries, Notch3 is the predominant receptor on VSMC and, signalling is initiated upon binding to its ligand, Jagged1. However, little is known on how ligand presenting strategies affect Notch signalling and subsequently upregulation of smooth muscle cell differentiation. In this study, using human coronary artery smooth muscle cells (HCASMC) and human coronary artery endothelial cells (HCAEC), we show several lines of evidence that direct heterocellular cell-cell contact is necessary for VSMC differentiation via Notch3 signalling. First, neither the addition of soluble Jagged1 nor Jagged1 immobilized to protein G beads induced HCASMC differentiation in culture. Second, despite the upregulation of Notch3 expression, EC-conditioned medium failed to induce HCASMC differentiation. However, when HCASMC and HCAEC were co-cultured either on opposite sides of porous membrane or when these cells were co-cultured directly, both Notch3 and VSMC differentiation marker proteins were upregulated. These upregulations were abrogated by Jagged1-specific siRNA. This study provides the first direct evidence that contact of HCASMC and HCAEC is required for regulating smooth muscle cell differentiation. These findings may have clinical importance and therapeutic potential for modulating vascular SMC phenotype during various cardiovascular disease states and in tissue engineering.

Keywords
Notch3 signalling; Jagged1; Co-culture; siRNA; Differentiation marker proteins; Vascular smooth muscle cell
First Page Preview
The role of endothelial cell-bound Jagged1 in Notch3-induced human coronary artery smooth muscle cell differentiation
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 8, March 2012, Pages 2462–2472
Authors
, , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us