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

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

Jingping Liu,1 Shuyun Liu,1 Younan Chen,1 Xiaojun Zhao,2 Yanrong Lu,1 Jingqiu Cheng1 1Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, 2Laboratory of Nanomedicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China...

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Autores principales: Liu JP, Liu SY, Chen YN, Zhao XJ, Lu YR, Cheng JQ
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/e982235b9f3242919abebe54b10ba1c9
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spelling oai:doaj.org-article:e982235b9f3242919abebe54b10ba1c92021-12-02T05:09:59ZFunctionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway1178-2013https://doaj.org/article/e982235b9f3242919abebe54b10ba1c92015-05-01T00:00:00Zhttp://www.dovepress.com/functionalized-self-assembling-peptide-improves-ins-1-beta-cell-functi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jingping Liu,1 Shuyun Liu,1 Younan Chen,1 Xiaojun Zhao,2 Yanrong Lu,1 Jingqiu Cheng1 1Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, 2Laboratory of Nanomedicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Islet transplantation is considered to be a curative treatment for type 1 diabetes mellitus. However, disruption of the extracellular matrix (ECM) leads to β-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 β-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 β-cells by upregulation of E-cadherin, fibronectin, and collagen IV. KLD-F also enhanced glucose-stimulated insulin secretion and expression of β-cell function genes, including Glut2, Ins1, MafA, and Pdx-1 in INS-1 cells. Moreover, KLD-F promoted proliferation of INS-1 β-cells and upregulated Ki67 expression by mediating cell cycle progression. In addition, KLD-F improved β-cell function and proliferation via an integrin/focal adhesion kinase/extracellular signal-regulated kinase/cyclin D pathway. This study highlights the fact that the β-cell-ECM interaction reestablished with this functionalized self-assembling peptide is a promising method to improve the therapeutic efficacy of islet transplantation. Keywords: extracellular matrix, self-assembling peptide, islet transplantation, β-cell proliferation, insulin secretionLiu JPLiu SYChen YNZhao XJLu YRCheng JQDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3519-3531 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Liu JP
Liu SY
Chen YN
Zhao XJ
Lu YR
Cheng JQ
Functionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
description Jingping Liu,1 Shuyun Liu,1 Younan Chen,1 Xiaojun Zhao,2 Yanrong Lu,1 Jingqiu Cheng1 1Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, 2Laboratory of Nanomedicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Islet transplantation is considered to be a curative treatment for type 1 diabetes mellitus. However, disruption of the extracellular matrix (ECM) leads to β-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 β-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 β-cells by upregulation of E-cadherin, fibronectin, and collagen IV. KLD-F also enhanced glucose-stimulated insulin secretion and expression of β-cell function genes, including Glut2, Ins1, MafA, and Pdx-1 in INS-1 cells. Moreover, KLD-F promoted proliferation of INS-1 β-cells and upregulated Ki67 expression by mediating cell cycle progression. In addition, KLD-F improved β-cell function and proliferation via an integrin/focal adhesion kinase/extracellular signal-regulated kinase/cyclin D pathway. This study highlights the fact that the β-cell-ECM interaction reestablished with this functionalized self-assembling peptide is a promising method to improve the therapeutic efficacy of islet transplantation. Keywords: extracellular matrix, self-assembling peptide, islet transplantation, β-cell proliferation, insulin secretion
format article
author Liu JP
Liu SY
Chen YN
Zhao XJ
Lu YR
Cheng JQ
author_facet Liu JP
Liu SY
Chen YN
Zhao XJ
Lu YR
Cheng JQ
author_sort Liu JP
title Functionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_short Functionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_full Functionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_fullStr Functionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_full_unstemmed Functionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway
title_sort functionalized self-assembling peptide improves ins-1 β-cell function and proliferation via the integrin/fak/erk/cyclin pathway
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/e982235b9f3242919abebe54b10ba1c9
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