EGF Family (EGFs and Receptors)

The Role of Epidermal Growth Factor (EGF)

Epidermal growth factor (EGF) is a multifunctional growth factor that plays a crucial role in cell growth, migration, and differentiation. It achieves these effects by binding to its receptor (EGFR) and regulating gene expression, thus contributing to the normal metabolism of epithelial cells.

The Role of Epidermal Growth Factor Receptor (EGFR)

Epidermal Growth Factor Receptor (EGFR), also known as EGFR, ErbB-1, or HER1, is a member of the HER (epidermal growth factor receptor) family. This family consists of HER1 (erbB1, EGFR), HER2 (erbB2, NEU), HER3 (erbB3), and HER4 (erbB4). The HER family plays a crucial role in regulating various cellular physiological processes.

EGFR is widely expressed on the cell surface of mammalian epithelial cells, fibroblasts, glial cells, keratinocytes, and others. The EGFR signaling pathway is involved in essential physiological processes such as cell growth, proliferation, and differentiation.

EGFR is a receptor for epidermal growth factor (EGF), responsible for cell proliferation and signal transduction. It belongs to the ErbB receptor family, which includes EGFR (ErbB-1), HER2/c-neu (ErbB-2), Her 3 (ErbB-3), and Her 4 (ErbB-4). Mutations or overexpression of EGFR are commonly associated with tumors. EGFR is a glycoprotein and belongs to the tyrosine kinase receptor type. It is located on the cell membrane, spanning it, and has a molecular weight of 170 kDa. Activation of EGFR occurs when it binds to ligands such as EGF and TGFα (transforming growth factor α). Upon activation, EGFR undergoes a conversion from a monomer to a dimer, although evidence suggests that dimers may exist prior to activation. EGFR can also be activated through interaction with other members of the ErbB receptor family, such as ErbB2/Her2/neu.

Following dimerization, EGFR can activate intracellular kinase pathways, including activation sites such as Y992, Y1045, Y1068, Y1148, and Y1173. Autophosphorylation at these sites leads to downstream phosphorylation events, involving MAPK, Akt, and JNK pathways, which ultimately induce cell proliferation. Receptor activation is also critical for skin immunity.

Biological Function of Epidermal Growth Factor (EGF)

EGF, as a growth factor, plays a crucial role in maintaining the dynamic balance of tissue cell proliferation and apoptosis. Imbalances in EGF levels, either insufficient or excessive, can lead to the development of diseases. EGF binds to EGFR and exerts its biological effects on target cells. The activation of receptor tyrosine kinases is the initial step in EGF function. Notably, the effects of EGF are not species-specific; human and mouse EGF have the same impact on human fibroblasts, and their binding affinity to the receptor is also identical.

1. Effect of EGF on Trauma

Wound healing is a complex biological process, and EGF plays a significant role in this process. EGF promotes mitosis and stimulates anabolism in tissues derived from both ectoderm and endoderm, thereby accelerating the healing of wounds and burns.

2. Regulation of EGF on Tumor Cells

Tumor cells exhibit varied responses to EGF. Some tumor cells can proliferate through autocrine mechanisms, while the growth of other tumor cells is inhibited by EGF. Low doses of EGF generally stimulate cell growth, while high doses can suppress the growth of specific cells.

3. Protective Effect of EGF on Stress Ulcers

Under stress conditions, sympathetic nerve stimulation causes vasoconstriction in the visceral blood vessels of the digestive system, leading to reduced blood flow and resulting in ischemia and hypoxia, which are significant factors contributing to gastric mucosal damage. EGF increases gastric mucosal blood flow and enhances the resistance of gastric mucosal cells against gastric acid erosion, thereby providing protective effects against stress ulcers.

EGFR signaling pathway

The EGFR (Epidermal Growth Factor Receptor) protein is a member of the receptor tyrosine kinases (RTKs) family. It is capable of activating two signaling pathways: the RAS-RAF-MEK-ERK pathway, which is involved in cell proliferation (also known as the MAPK/ERK pathway), and the PI3K-AKT-mTOR pathway, which is involved in cell survival. The RAS-RAF-MEK-ERK pathway regulates gene transcriptional activity and the cell cycle, while the PI3K-AKT-mTOR pathway triggers anti-apoptotic signals. Therefore, the EGFR receptor protein plays a critical role in both cell proliferation and survival.

Clinical Significance of the EGF Family

EGF (Epidermal Growth Factor) holds significant clinical significance and application value in various domains.

1. Treatment of Skin Diseases

EGF finds wide application in the treatment of skin diseases. Its ability to promote the proliferation and repair of epithelial cells makes it a valuable component in the treatment of skin injuries like burns, wounds, ulcers, and surgical incisions. EGF aids in wound healing, tissue regeneration, and expedites skin recovery.

2. Anti-Aging and Beauty

EGF is recognized as an effective anti-aging ingredient as it stimulates the growth and repair of skin cells. Incorporating EGF into skincare products can enhance skin elasticity, diminish wrinkles and fine lines, resulting in a more youthful and smooth appearance.

3. Tumor Therapy

EGF and its receptor EGFR are observed to be abnormally expressed or overactivated in various tumors. Consequently, targeting the EGF-EGFR signaling pathway has become a significant approach in tumor therapy. Several anti-EGF-EGFR drugs, such as targeted antibodies and tyrosine kinase inhibitors, have been successfully employed in the treatment of malignant tumors including lung cancer, colorectal cancer, and breast cancer.

4. Tissue Engineering and Regenerative Medicine

EGF possesses considerable application potential in the realm of tissue engineering and regenerative medicine. Leveraging the growth-promoting effects of EGF, cells and tissues can be cultured in vitro to facilitate the repair and regeneration of damaged tissues and organs. This advancement holds profound implications for trauma recovery, organ transplantation, and disease treatment.

Summary of the EGF Family

The EGF family comprises vital cell growth factors that play a crucial role in regulating biological processes like cell growth, differentiation, and survival through interaction with EGFR (Epidermal Growth Factor Receptor). In-depth research on the EGF family aids in comprehending their functions in both normal physiological and pathological processes. Moreover, it offers novel avenues and strategies for the treatment of associated diseases.