IGFBP7 - Insulin Like Growth Factor Binding Protein 7 | Elisa - Clia - Antibody - Protein

Background:

Insulin-like Growth Factor Binding Protein 7 (IGFBP7), also known as Mac25 or IGFBP-rP1, is a member of the insulin-like growth factor binding protein (IGFBP) family. IGFBP7 is a secreted protein that binds to insulin-like growth factors (IGFs), including IGF-I and IGF-II, with high affinity. It consists of an N-terminal domain responsible for IGF binding and a C-terminal domain involved in interactions with other proteins and extracellular matrix components. IGFBP7 regulates the bioavailability and activity of IGFs by binding to them in the extracellular environment. This binding can modulate the interaction of IGFs with their cell surface receptors, affecting downstream signaling pathways involved in cell growth, differentiation, and survival. In addition to its role in IGF regulation, IGFBP7 has been implicated in various cellular processes, including apoptosis, senescence, and tissue remodeling. Its functions appear to be context-dependent and can vary depending on the cellular microenvironment and signaling cues. IGFBP7 is expressed in various tissues and cell types, including the liver, kidney, heart, and certain types of cancer cells. Its expression can be regulated by factors such as growth factors, hormones, and cellular stress. Altered expression of IGFBP7 has been reported in various types of cancer, where it can have both tumor-suppressive and tumor-promoting effects depending on the context. For example, IGFBP7 has been shown to inhibit cell proliferation and induce apoptosis in certain cancer cells, while in other contexts, it may promote tumor invasion and metastasis. IGFBP7 has been also implicated in the pathogenesis of cardiovascular diseases such as atherosclerosis and heart failure, where it may influence vascular remodeling, inflammation, and fibrosis.

Protein Structure:

IGFBP7 is a secreted protein that consists of an N-terminal IGFBP domain, a Kazal-type serine protease inhibitor domain, and a C-terminal domain unique to this protein. The combination of these domains allows IGFBP7 to interact with IGFs, other growth factors, and extracellular matrix components, thereby influencing various signaling pathways.

Classification and Subtypes:

IGFBP7 is part of the IGFBP family, which includes six high-affinity IGFBPs (IGFBP1-6) and several low-affinity binding proteins like IGFBP7. Unlike the high-affinity IGFBPs, IGFBP7 has a broader range of biological activities due to its ability to bind other growth factors and matrix components.

Function and Biological Significance:

• Regulation of Cell Growth: IGFBP7 can inhibit cell proliferation and promote apoptosis in various cell types, acting as a tumor suppressor in certain contexts.
• Angiogenesis: IGFBP7 is involved in the regulation of angiogenesis, the process by which new blood vessels form from pre-existing vessels, which is crucial in both normal physiology and pathological conditions like cancer.
• Cell Adhesion and Migration: IGFBP7 influences cell adhesion and migration by interacting with extracellular matrix components, thereby playing a role in tissue remodeling and repair.
• Metabolic Regulation: IGFBP7 modulates metabolic processes and has been implicated in insulin sensitivity and glucose metabolism.

Interactions:

• IGFs: Although IGFBP7 has a low affinity for IGFs, it can still interact with IGF-1 and IGF-2, modulating their availability and activity.
• Extracellular Matrix Components: IGFBP7 binds to extracellular matrix proteins such as fibronectin, influencing cell adhesion and migration.
• Growth Factors: IGFBP7 interacts with a variety of growth factors, including vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β), modulating angiogenesis and other cellular responses.

Clinical Issues:

• Cancer: IGFBP7 acts as a tumor suppressor in various cancers, including melanoma, breast cancer, and colorectal cancer. Loss or downregulation of IGFBP7 is often associated with tumor progression and poor prognosis.
• Cardiovascular Diseases: IGFBP7 is involved in the regulation of cardiovascular function and has been linked to conditions such as heart failure and hypertension. It is being investigated as a biomarker for the diagnosis and prognosis of heart failure.
• Metabolic Disorders: Altered levels of IGFBP7 are associated with metabolic conditions like diabetes and obesity, where it may influence insulin sensitivity and glucose metabolism.

Summary:

IGFBP7 is a multifaceted protein that, while having low affinity for IGFs, plays crucial roles in cell growth regulation, angiogenesis, cell adhesion, and migration. It acts as a tumor suppressor in various cancers and is implicated in cardiovascular and metabolic diseases. Understanding IGFBP7's diverse interactions and functions highlights its potential as a therapeutic target and biomarker for several pathological conditions.