Functionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the...

Area of Science:

• Biomaterials Science
• Cell Biology
• Endocrinology

Background:

• Type 1 diabetes mellitus (T1DM) treatment often involves islet transplantation.
• Disruption of the extracellular matrix (ECM) impairs beta-cell function and graft survival post-transplantation.
• Developing biomaterials to support beta-cells within the transplanted graft is crucial.

Purpose of the Study:

• To develop a functionalized self-assembling peptide (KLD-F) mimicking ECM motifs.
• To evaluate KLD-F's impact on beta-cell function, proliferation, and survival in a 3D culture model.
• To investigate the underlying molecular mechanisms of KLD-F's therapeutic effects.

Main Methods:

• KLD-F peptide synthesis and characterization using atomic force microscopy and rheology.
• Three-dimensional cell culture of INS-1 beta-cells within KLD-F hydrogels.
• Assessment of ECM remodeling, cell adhesion molecules (E-cadherin), ECM proteins (fibronectin, collagen IV), and beta-cell function genes (Glut2, Ins1, MafA, Pdx-1).
• Analysis of cell proliferation (Ki67) and signaling pathways (integrin/FAK/ERK/cyclin D).

Main Results:

• KLD-F self-assembled into a nanofibrous hydrogel scaffold under physiological conditions.
• KLD-F enhanced ECM remodeling and INS-1 beta-cell adhesion by upregulating key proteins.
• KLD-F significantly improved glucose-stimulated insulin secretion and expression of essential beta-cell function genes.
• KLD-F promoted beta-cell proliferation via cell cycle progression and modulated the integrin/FAK/ERK/cyclin D pathway.

Conclusions:

• Functionalized self-assembling peptide KLD-F effectively mimics the native ECM environment.
• KLD-F supports beta-cell function, proliferation, and survival by enhancing cell-ECM interactions.
• KLD-F represents a promising therapeutic strategy to improve islet transplantation outcomes in type 1 diabetes.