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

© 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 EC...

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Main Authors: Liu, J., Liu, S., Chen, Younan, Zhao, X., Lu, Y., Cheng, J.
Format: Journal Article
Published: 2015
Online Access:http://hdl.handle.net/20.500.11937/39904
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author Liu, J.
Liu, S.
Chen, Younan
Zhao, X.
Lu, Y.
Cheng, J.
author_facet Liu, J.
Liu, S.
Chen, Younan
Zhao, X.
Lu, Y.
Cheng, J.
author_sort Liu, J.
building Curtin Institutional Repository
collection Online Access
description © 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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spelling curtin-20.500.11937-399042017-09-13T15:08:56Z Functionalized self-assembling peptide improves INS-1 ß-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway Liu, J. Liu, S. Chen, Younan Zhao, X. Lu, Y. Cheng, J. © 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/39904 10.2147/IJN.S80502 unknown
spellingShingle Liu, J.
Liu, S.
Chen, Younan
Zhao, X.
Lu, Y.
Cheng, J.
Functionalized self-assembling peptide improves INS-1 ß-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title Functionalized self-assembling peptide improves INS-1 ß-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_full Functionalized self-assembling peptide improves INS-1 ß-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_fullStr Functionalized self-assembling peptide improves INS-1 ß-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_full_unstemmed Functionalized self-assembling peptide improves INS-1 ß-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_short Functionalized self-assembling peptide improves INS-1 ß-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_sort functionalized self-assembling peptide improves ins-1 ß-cell function and proliferation via the integrin/fak/erk/cyclin pathway
url http://hdl.handle.net/20.500.11937/39904