Inhibited effect of an RGD peptide hydrogel on the expression of β1‐integrin, FAK, and Akt in Tenon's capsule fibroblasts

Abstract

Tenon's capsule fibroblasts are the main cellular components of filtration tract scar that limit the success rate of glaucoma filtration surgery. Scar formation results from infiltration and proliferation of fibroblasts into damaged areas, meanwhile synthesis of extracellular matrix glycoproteins. Integrins are cell surface receptors for extracellular molecules that mediate cell adhesion, spreading, migration, and invasion. They bind their ligands often through recognition of short amino‐acid sequences—arginine‐glycine‐aspartic acid (RGD). Peptides that contain RGD sequence can compete with RGD containing insoluble matrix proteins for binding to the integrin receptor and thus prevent the downstream signaling pathway. Increasing evidence supports that β1‐integrin/focal adhesion kinase (FAK)/Akt signal pathway plays an important role in fibrogenesis and scar formation in different tissues. In consideration of advantages of peptide hydrogel, that is well biocompatibility, gel state, degradability, good drug loading, we designed and fabricated an RGD peptide hydrogel, and hypothesized that it could inhibit the expression of β1‐integrin, FAK, and Akt in Tenon's capsule fibroblasts. Rheology results showed that 1% wt Fmoc‐FFGGRGD peptide solution could self‐assemble into hydrogel. Western blot analysis revealed that there were statistical differences between control group and 1% wt group in β1‐integrin/β‐actin, FAK/β‐actin, Akt/β‐actin respectively (*p < .05). The relative mRNA expression of β1‐integrin, FAK, Akt in control group and 1% wt group were also statistically different respectively (*p < .05). We proved that 1% wt Fmoc‐FFGGRGD self‐assembly peptide hydrogel could inhibit the expression of β1‐integrin, FAK and Akt in Tenon's capsule fibroblasts. It is a promising way to solve scar formation of glaucoma filter channel.

Self-Assembled Peptide Nanostructures for ECM Biomimicry

“…Finally, a Fmoc-FFGGRGD-based hydrogel proved that the RGD sequence also interferes with gene expression in Tenon's capsule fibroblasts, in particular reducing the β 1 -integrin, FAK, and Akt expression in order to inhibit fibrogenesis and scar formation that limits the success of glaucoma filtration surgery [70].…”

Glaucoma Treatment and Hydrogel: Current Insights and State of the Art

“…Hydrogels minimize inflammation and hinder fibroblasts’ adhesion to scleral tissue, as confirmed by the reduction of connective tissue growth factor (CTGF), a peptide promoting the formation of fibrosis and scarring in ocular tissues [ 153 ]. Chen et al [ 154 ] investigated in vitro hydrogels containing different concentrations of the arginine-glycine-aspartic acid (RGD) sequence (0.25; 0.5 and 1%). This sequence induces competition with proinflammatory proteins of the extracellular membrane for binding to integrins, cellular receptors that promote migration, and the proliferation of fibroblasts without cytotoxicity.…”

Scaffold Adhering to Peptide-Based Biomimetic Extracellular Matrix Composite Nanobioglass Promotes the Proliferation and Migration of Skin Fibroblasts Through the GSK-3β/β-Catenin Signaling Axis

“…This interaction plays an essential role in regulating various cellular processes such as proliferation, migration, growth factor sequestration, and cell signaling through cell surface receptors. 12 …”

“…This interaction plays an essential role in regulating various cellular processes such as proliferation, migration, growth factor sequestration, and cell signaling through cell surface receptors. 12 Yakovlev et al conducted experiments demonstrating that RGD promotes wound closure in HUVEC by interacting with the αC domain of the HUVEC integrin binding site. 13 In our study, we utilized nanobioactive glass as a cell scaffold to investigate the migration and healing of fibroblasts.…”