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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

Effects of Arg-Gly-Asp-modified elastin-like polypeptide on pseudoislet formation via up-regulation of cell adhesion molecules and extracellular matrix proteins
Lee, KM[Lee, Kyeong-Min]Jung, GS[Jung, Gwon-Soo]Park, JK[Park, Jin-Kyu]Choi, SK[Choi, Seong-Kyoon]Jeon, WB[Jeon, Won Bae]
DGIST Authors
Lee, KM[Lee, Kyeong-Min]; Jung, GS[Jung, Gwon-Soo]; Park, JK[Park, Jin-Kyu]; Choi, SK[Choi, Seong-Kyoon]; Jeon, WB[Jeon, Won Bae]
Issue Date
Acta Biomaterialia, 9(3), 5600-5608
Article Type
Amino Acid SequenceAnimal CellAnimalsArginyl-Glycyl-Aspartic AcidBeta-CellsCadherinsCell Adhesion MoleculeCell Adhesion MoleculesCell ProliferationCell ShapeCell SurvivalCell ViabilityCollagenCollagen Type 2Collagen Type 4Connexin-36ConnexinsControlled StudyE-CadherinElastinExtracellular MatrixExtracellular Matrix ProteinsFibronectinFibronectinsGene Expression RegulationInsulinInsulin ReleaseInsulin SecretionIslets of LangerhansLamininMiceMonolayer CultureMouseNon-HumanNucleotide SequenceOligopeptidesPancreas Islet Beta CellPriority JournalProtein ExpressionPseudoisletRNA, MessengerRNA, Small InterferingScleroproteinSmall Interfering RnaSpheroids, CellularTransition TemperatureUp-RegulationUpregulation
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.
Elsevier Ltd
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Companion Diagnostics and Medical Technology Research Group1. Journal Articles

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