title: Effects of Arg-Gly-Asp-modified elastin-like polypeptide on pseudoislet formation via up-regulation of cell adhesion molecules and extracellular matrix proteins.
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)](20)WPC, 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 7days' culture, the proliferation rate of the cells within a pseudoislet was similar to that of monolayer culture. Under high glucose (25mM), 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.
authors.affiliation: Laboratory of Biochemistry and Cellular Engineering, Division of NanoBio Technology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, South Korea.
authors.forename: Kyeong-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Gwon-Soo
authors.initials: GS
authors.lastname: Jung
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Seong-Kyoon
authors.initials: SK
authors.lastname: Choi
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Jeon
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D004549:Elastin / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000254:growth & development*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects; D044366:Transition Temperature; D015854:Up-Regulation / Q000187:drug effects*; D000097004:Gap Junction delta-2 Protein
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D003094:Collagen; D017630:Connexins; D004549:Elastin; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007328:Insulin; D007797:Laminin; D009842:Oligopeptides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000097004:Gap Junction delta-2 Protein; C047981:arginyl-glycyl-aspartic acid