Genetically Engineered Epidermal Growth Factor Conjugate Crosses Cell Membrane

Abstract

Epidermal growth factor (EGF) is a well-known pleiotropic growth factor in mammal, and has been attempted to be used in many different fields. However, the application of EGF is limited because of its poor cell permeation. In order to increase membrane permeation ability of EGF, a genetically modified recombinant EGF (GST-TAT-EGF) was prepared through conjugation of EGF with two protein transduction domains, glutathione-S-transferase and TAT47-57. The results showed that the GST-TAT-EGF fusion protein exhibited higher ability in biomembrane penetration than that of the EGF alone. The results also implied that two different mechanisms (EGF receptor-mediated endocytosis and direct penetration) might be involved in GST-TAT-EGF transmembrane delivery.

Protective effects of skin permeable epidermal and fibroblast growth factor against ultraviolet‐induced skin damage and human skin wrinkles

“…Also, transduced GST‐TAT‐EGF fusion protein significantly stimulated cell proliferation. However, native EGF and GST‐TAT‐EGF fusion protein had similar effects on cell proliferation . In agreement with our results, transduced PTD‐EGF and FGF1 proteins markedly increased cell proliferation.…”

“…Many studies have demonstrated that the delivery of exogenous full‐length proteins into living cells via protein transduction, facilitated by protein transduction domains (PTDs), can be used as a successful tool for the therapeutic application of proteins . Studies by this research team have demonstrated both in vitro and in vivo the therapeutic effects of fusion proteins against a variety of diseases including those afflicting skin …”

PEP-1-PON1 Protein Regulates Inflammatory Response in Raw 264.7 Macrophages and Ameliorates Inflammation in a TPA-Induced Animal Model

“…Although the mechanism requires further study, many studies have demonstrated that therapeutic PTD fusion proteins delivered into cells and tissues protect against cell toxicity. Also, PTD fusion proteins have potential in the treatment of various diseases [22]–[27]. In a previous study, we also demonstrated that PEP-1 fusion proteins transduced into cells [28]–[36].…”

“…The use of protein as therapeutic agents is limited by their molecular size, low permeability and biochemical characteristics [21], [22]. However, many studies have shown that the delivery of therapeutic proteins to cells and tissues using protein transduction domains (PTDs) is a powerful tool in clinical protein application [21]–[27].…”