Rice-derived peptide PG9 modulates inflammation and promotes keratinocyte migration via EGFR and PI3K/AKT/mTOR
Background
Chronic wounds and impaired tissue regeneration pose significant clinical challenges, often exacerbated by persistent inflammation. Current treatments frequently fall short, highlighting a need for novel, safe, and effective therapeutic agents. Tumor necrosis factor (TNF)-α and interferon (IFN)-γ are key pro-inflammatory cytokines that can induce keratinocyte injury, impairing the crucial proliferation phase of wound healing. Food-derived bioactive peptides offer a promising avenue due to their potential health benefits and favorable safety profiles, making them attractive candidates for natural skin repair strategies.
Study Design
Researchers investigated rice protein hydrolysates (< 3 kDa) and their derived peptides for protective effects against TNF-α/IFN-γ-induced injury in human keratinocyte cells (HaCaT). Hydrolysates were screened for enhanced cell viability and migration. Five peptides were identified using LC-MS/MS and in-silico analysis. The most active peptide, PG9 (PSWVAFTGG), was then tested for its ability to improve viability of damaged cells, promote migration, and modulate gene expression via qPCR. Molecular dynamics simulations were employed to predict interactions with the epidermal growth factor receptor (EGFR).
Results
Rice protein hydrolysates significantly enhanced HaCaT cell viability and migration. Among five identified peptides, PG9 (PSWVAFTGG) exhibited the greatest activity, significantly improving the viability of damaged cells. PG9 markedly promoted keratinocyte migration, a crucial step in wound closure. Molecular dynamics simulations revealed that PG9 formed stable hydrogen-bonds with key residues (Lys745 and Asp855) within the EGFR binding site, suggesting a direct interaction. This interaction implies involvement in EGFR-mediated wound healing signaling. Furthermore, PG9 significantly downregulated the mRNA expression of several pro-inflammatory cytokines: Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES), Interleukin (IL)-1β, IL-6, and IL-23.
Key Findings
- Rice-derived peptide PG9 (PSWVAFTGG) significantly improved viability of TNF-α/IFN-γ-damaged human keratinocytes.
- PG9 markedly promoted keratinocyte migration, a key process in wound healing.
- PG9 downregulated mRNA expression of pro-inflammatory cytokines including
RANTES,IL-1β,IL-6, andIL-23. - Molecular dynamics simulations showed PG9 binds to the
EGFRvia Lys745 and Asp855. - PG9 regulated the
PI3K/AKT/mTORpathway by reducing expression ofPI3K,AKT,mTORand inhibitingAKTphosphorylation.
Why It Matters
This study identifies PG9 as a promising natural agent for skin repair, offering a potential therapeutic strategy for inflammatory skin conditions and chronic wounds. The dual action of reducing inflammation and promoting keratinocyte migration, coupled with its interaction with EGFR and modulation of the PI3K/AKT/mTOR pathway, suggests a comprehensive mechanism of action. This research provides a strong foundation for developing rice-derived peptides into topical formulations for wound healing. While currently an in-vitro finding, it paves the way for future preclinical animal studies to validate efficacy and safety in a living system, moving closer to a usable protocol for human application.
pg9
wound-healing
keratinocytes
inflammation
egfr
pi3k-akt-mtor