Neurotrophins

PEDF is a 50 kDa glycoprotein consisting of 418 amino acids . It is widely expressed in various tissues, including the retina, liver, adipose tissue, bone, and muscle . PEDF exhibits anti-angiogenic, anti-tumorigenic, anti-inflammatory, and neurotrophic properties . Its expression is highest in the liver and adipose tissue, with notable expression in the eye, heart, and pancreas .

PEDF plays a crucial role in inhibiting angiogenesis, promoting cell differentiation, and protecting against oxidative stress . It is involved in immune responses by modulating inflammation and inhibiting the migration and proliferation of endothelial cells . PEDF also contributes to pathogen recognition and immune regulation by interacting with various immune cells .

PEDF exerts its effects through multiple mechanisms, including binding to specific receptors and interacting with other molecules . It binds to collagen I, affecting endothelial cell adhesion and angiogenesis . PEDF also interacts with receptors such as PEDF-R, which mediates its anti-angiogenic and neurotrophic effects . Downstream signaling cascades involve the inhibition of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) activity .

The expression and activity of PEDF are regulated at both transcriptional and post-translational levels . Transcriptional regulation involves various factors, including hormonal regulation by estrogen and progesterone . Post-translational modifications, such as phosphorylation, also play a role in modulating PEDF activity . Additionally, PEDF levels decline with aging and in certain pathological conditions .

PEDF has significant potential in biomedical research, diagnostic tools, and therapeutic strategies . It is being explored as a therapeutic candidate for conditions such as choroidal neovascularization, heart disease, cancer, and sensorineural hearing loss . PEDF’s anti-inflammatory and anti-angiogenic properties make it a promising agent for treating age-related macular degeneration and diabetic retinopathy .

Throughout the life cycle, PEDF plays a vital role in development, aging, and disease . During development, PEDF regulates angiogenesis and cell differentiation . In adulthood, it maintains tissue homeostasis and protects against oxidative stress . With aging, PEDF levels decline, contributing to age-related diseases such as cancer and cardiovascular disorders . PEDF’s involvement in bone homeostasis and prevention of bone resorption highlights its importance in maintaining skeletal health .