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    Functionalized self-assembling peptide improves INS-1 ß-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway

    Access Status
    Open access via publisher
    Authors
    Liu, J.
    Liu, S.
    Chen, Younan
    Zhao, X.
    Lu, Y.
    Cheng, J.
    Date
    2015
    Type
    Journal Article
    
    Metadata
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    Citation
    Liu, J. and Liu, S. and Chen, Y. and Zhao, X. and Lu, Y. and Cheng, J. 2015. Functionalized self-assembling peptide improves INS-1 ß-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway. International Journal of Nanomedicine. 10: pp. 3519-3531.
    Source Title
    International Journal of Nanomedicine
    DOI
    10.2147/IJN.S80502
    ISSN
    1176-9114
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/39904
    Collection
    • Curtin Research Publications
    Abstract

    © 2015 Liu et al. Islet transplantation is considered to be a curative treatment for type 1 diabetes mellitus. However, disruption of the extracellular matrix (ECM) leads to ß-cell destruction and graft dysfunction. In this study, we developed a functionalized self-assembling peptide, KLD-F, with ECM mimic motifs derived from fibronectin and collagen IV, and evaluated its effect on ß-cell function and proliferation. Atomic force microscopy and rheological results showed that KLD-F could self-assemble into a nanofibrous scaffold and change into a hydrogel in physiological saline condition. In a three-dimensional cell culture model, KLD-F improved ECM remodeling and cell-cell adhesion of INS-1 ß-cells by upregulation of E-cadherin, fibronectin, and collagen IV. KLD-F also enhanced glucose-stimulated insulin secretion and expression of ß-cell function genes, including Glut2, Ins1, MafA, and Pdx-1 in INS-1 cells. Moreover, KLD-F promoted proliferation of INS-1 ß-cells and upregulated Ki67 expression by mediating cell cycle progression. In addition, KLD-F improved ß-cell function and proliferation via an integrin/focal adhesion kinase/extracellular signal-regulated kinase/cyclin D pathway. This study highlights the fact that the ß-cell-ECM interaction reestablished with this functionalized self-assembling peptide is a promising method to improve the therapeutic efficacy of islet transplantation.

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