Insulin-like growth factor-binding protein 7 (IGFBP7) is a protein naturally present throughout the human body. IGFBP7 carries out several functions that contribute to maintaining the body’s balance. This protein plays a role in various biological processes, influencing how cells grow, divide, and respond to stress.
Biological Function in the Body
IGFBP7’s name provides insight into its primary biological function: it is an “Insulin-like growth factor-binding protein.” Its main role involves interacting with Insulin-like Growth Factors (IGFs), specifically IGF-1 and IGF-2. These IGFs promote cell growth and division.
IGFBP7 binds to these IGFs, which prevents them from fully interacting with their receptors on cell surfaces. This binding reduces growth-promoting signals, acting as a “brake pedal” on cell activity. By modulating IGF availability, IGFBP7 helps maintain balance in processes such as cell division, cell growth, and programmed cell death (apoptosis). This regulatory role is important to normal tissue development and repair.
Use as a Kidney Health Biomarker
A biomarker is a measurable indicator of a biological state or condition within the body. In the context of kidney health, IGFBP7 serves as a biomarker for Acute Kidney Injury (AKI), a sudden and often severe decline in kidney function. AKI can occur due to various stressors, including reduced blood flow, certain medications, or infections, leading to kidney cell damage.
When kidney cells experience stress or injury, they release IGFBP7, often alongside another protein called tissue inhibitor of metalloproteinases-2 (TIMP-2). The release of these proteins signals a “stop” to the cell cycle, aiming to prevent further damage and allow for cellular repair. Measuring IGFBP7 levels, typically in urine, provides an early indication of kidney cell stress before extensive damage occurs or before changes in traditional markers like creatinine become apparent.
Monitoring IGFBP7 levels, particularly in combination with TIMP-2, helps healthcare providers predict a patient’s risk of developing moderate to severe AKI within 12 hours of measurement. This predictive capability allows for earlier intervention strategies, potentially improving patient outcomes. The FDA has approved a specific diagnostic test, often referred to as the NephroCheck test, which measures both IGFBP7 and TIMP-2 in urine to assess AKI risk in hospitalized patients.
Involvement in Cancer Processes
Beyond its general role in regulating cell growth, IGFBP7 also participates in the body’s defense against cancer. This protein often acts as a tumor suppressor, preventing the uncontrolled cell growth characteristic of cancerous tumors. IGFBP7 achieves this by inducing cell cycle arrest or promoting programmed cell death in abnormal cells.
In healthy tissues, the presence of IGFBP7 helps to maintain cellular order and prevent the proliferation of damaged or mutated cells. However, in several types of cancer, its production or function is reduced or silenced. This allows cancer cells to evade normal growth controls and continue to divide unchecked, contributing to tumor development and progression. For instance, reduced IGFBP7 expression has been observed in certain melanomas, gastric cancers, and colon cancers, where its absence can contribute to more aggressive tumor behavior.
Relationship with Cellular Aging
IGFBP7 is also involved in cellular senescence, a process where cells permanently stop dividing but remain metabolically active. Cellular senescence is a component of the aging process, contributing to age-related conditions.
IGFBP7 is one of the proteins that can induce this senescent state in cells. When cells encounter stress or damage, such as DNA damage or excessive growth signals, they can enter senescence as a protective measure. IGFBP7 contributes to this by activating specific cellular pathways that halt cell division and promote the senescent phenotype.
This role in senescence is distinct from its function in AKI, where it induces a temporary cell-cycle arrest to facilitate repair, and from its role in cancer, where it actively suppresses abnormal growth. By promoting senescence, IGFBP7 helps to clear out older, potentially harmful cells, thereby contributing to tissue health. This highlights IGFBP7’s multifaceted involvement in maintaining cellular equilibrium throughout life.