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Effects of Arg-Gly-Asp-modified elastin-like polypeptide on pseudoislet formation via up-regulation of cell adhesion molecules and extracellular matrix proteins

Title
Effects of Arg-Gly-Asp-modified elastin-like polypeptide on pseudoislet formation via up-regulation of cell adhesion molecules and extracellular matrix proteins
Author(s)
Lee, Kyeong-MinJung, Gwon-SooPark, Jin-KyuChoi, Seong-KyoonJeon, Won Bae
Issued Date
2013-03
Citation
Acta Biomaterialia, v.9, no.3, pp.5600 - 5608
Type
Article
Author Keywords
Beta-cellsPseudoisletInsulin secretionE-cadherinConnexin-36
Keywords
PANCREATIC BETA-CELLSINSULIN-SECRETIONISLET TRANSPLANTATIONBINDINGMODELCX36CA2+RGD
ISSN
1742-7061
Abstract
Extracellular matrix (ECM) plays an important role in controlling the β-cell morphology, survival and insulin secretary functions. An RGD-modified elastin-like polypeptide (RGD-ELP), TGPG[VGRGD(VGVPG) 6]20WPC, has been reported previously as a bioactive matrix. In this study, to investigate whether RGD-ELP affects β-cell growth characteristics and insulin secretion, β-TC6 cells were cultured on the RGD-ELP coatings prepared via thermally induced phase transition. On RGD-ELP, β-TC6 cells clustered into an islet-like architecture with high cell viability. Throughout 7 days' culture, the proliferation rate of the cells within a pseudoislet was similar to that of monolayer culture. Under high glucose (25 mM), β-TC6 pseudoislets showed up-regulated insulin gene expression and exhibited glucose-stimulated insulin secretion. Importantly, the mRNA and protein abundances of cell adhesion molecules (CAM) E-cadherin and connexin-36 were much higher in pseudoislets than in monolayer cells. The siRNA-mediated inhibition of E-cadherin or connexin-36 expression severely limited pseudoislet formation. In addition, the mRNA levels of collagen types I and IV, fibronectin and laminin were significantly elevated in pseudoislets. The results suggest that RGD-ELP promotes pseudoislet formation via up-regulation of the CAM and ECM components. The functional roles of RGD-ELP are discussed in respect of its molecular composition. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/3259
DOI
10.1016/j.actbio.2012.10.036
Publisher
Elsevier Ltd
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Appears in Collections:
Division of Biotechnology 1. Journal Articles
Companion Diagnostics and Medical Technology Research Group 1. Journal Articles

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