title: Functionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway.
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.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Younan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Laboratory of Nanomedicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016213:Cyclins / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016023:Integrins / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D051381:Rats
chemical_list: D016213:Cyclins; D016023:Integrins; D010455:Peptides; D051417:Focal Adhesion Kinase 1
keywords: extracellular matrix; insulin secretion; islet transplantation; self-assembling peptide; β-cell proliferation