FGF2 - Fibroblast Growth Factor 2 | Elisa - Clia - Antibody - Protein

Background:

Fibroblast Growth Factor 2 (FGF2), also known as basic Fibroblast Growth Factor (bFGF), is a member of the Fibroblast Growth Factor family of proteins. FGF2 is a potent mitogen that regulates cell proliferation, differentiation, and survival in various cell types.FGF2 is a small, secreted protein consisting of 155 amino acids. It contains a highly conserved core region composed of 23-24 kDa that binds to FGF receptors (FGFRs) and heparan sulfate proteoglycans (HSPGs) on the cell surface. FGF2 can exist in different isoforms, including a low molecular weight (LMW) form and a high molecular weight (HMW) form, which differ in their ability to bind HSPGs and their stability in the extracellular matrix. FGF2 acts as a potent mitogen for various cell types, including fibroblasts, endothelial cells, and stem cells. It stimulates cell proliferation by binding to and activating FGFRs, leading to the activation of intracellular signaling pathways such as the mitogen-activated protein kinase (MAPK) pathway. FGF2 plays also a critical role in angiogenesis,. FGF2's angiogenic activity is important in wound healing, tissue repair, and pathological conditions such as cancer.FGF2 is involved in wound healing and tissue regeneration by promoting the migration and proliferation of various cell types, including fibroblasts, keratinocytes, and endothelial cells. It stimulates the synthesis of extracellular matrix components and enhances tissue remodeling, contributing to the repair of injured tissues. FGF2 also plays a role in neuroprotection and neurogenesis in the central nervous system. It promotes the survival and proliferation of neural progenitor cells, stimulates neuronal differentiation, and enhances synaptic plasticity, which may have implications for brain repair and recovery after injury or disease.

Protein Structure:

FGF2 exists in multiple isoforms due to alternative translation initiation from different start codons within the same mRNA. The main isoforms include:

• Low Molecular Weight (LMW) Isoform: This isoform (18 kDa) is the most studied and primarily located in the cytoplasm and nucleus.
• High Molecular Weight (HMW) Isoforms: These isoforms (22-34 kDa) have additional N-terminal extensions and are primarily nuclear.

The FGF2 protein structure includes:

• A core region of about 140 amino acids forming a β-trefoil structure, crucial for receptor binding.
• Basic amino acid residues facilitating heparin and heparan sulfate binding, enhancing its stability and interaction with receptors.

Classification and Subtypes:

FGF2 is classified under the FGF family, which includes 22 members grouped into seven subfamilies based on sequence similarity and functional characteristics. FGF2 belongs to the FGF1 subfamily, which also includes FGF1 (acidic FGF).

Function and Biological Significance:

• Cell Proliferation and Differentiation: FGF2 stimulates the proliferation and differentiation of various cell types, including fibroblasts, endothelial cells, and neural cells.
• Angiogenesis: It is a potent angiogenic factor, promoting the formation of new blood vessels, essential for tissue growth and repair.
• Wound Healing: FGF2 enhances the repair process by stimulating cell migration, proliferation, and matrix remodeling.
• Neuroprotection and Neurogenesis: It supports the survival and growth of neurons and is involved in neurogenesis and brain development.
• Stem Cell Maintenance: FGF2 maintains the pluripotency of embryonic stem cells and supports the self-renewal of adult stem cells.

Interactions:

• FGFRs: FGF2 exerts its effects by binding to fibroblast growth factor receptors (FGFRs) 1-4. This binding activates various downstream signaling pathways, including MAPK/ERK, PI3K/Akt, and PLCγ, leading to its diverse biological effects.
• Heparan Sulfate Proteoglycans (HSPGs): HSPGs on cell surfaces and in the extracellular matrix modulate FGF2 activity by stabilizing the FGF2-FGFR complex and enhancing receptor binding.

Clinical Issues:

• Cancer: FGF2 is implicated in tumor growth, angiogenesis, and metastasis. Elevated levels of FGF2 are found in various cancers, including breast, prostate, and bladder cancer. Targeting FGF2 signaling is a potential therapeutic strategy in oncology.
• Fibrosis: Abnormal FGF2 signaling contributes to fibrotic diseases by promoting fibroblast proliferation and extracellular matrix production.
• Wound Healing Disorders: FGF2 therapy is explored for chronic wounds and ulcers due to its role in tissue repair and regeneration.
• Neurodegenerative Diseases: FGF2's neuroprotective properties make it a candidate for treating neurodegenerative conditions like Parkinson's and Alzheimer's disease.

Summary:

FGF2 is a multifunctional growth factor involved in cell proliferation, differentiation, angiogenesis, wound healing, and neuroprotection. It interacts with FGFRs and HSPGs to activate multiple signaling pathways. While playing critical roles in normal physiology, dysregulated FGF2 signaling is associated with cancer, fibrosis, and other pathological conditions. Understanding FGF2's functions and mechanisms provides insights into developing therapeutic interventions for various diseases.