Abstract
Angiopoietin-2, an important contributor to angiogenesis and vascular remodeling, is increasingly recognized in kidney research. This review explores clinical insights and experimental perspectives on angiopoietin-2 in kidney diseases. Traditionally seen as an antagonist of the Tie-2, which is a receptor tyrosine kinase of endothelial cells and some hematopoietic stem cells, angiopoietin-2 exerts both proangiogenic and antiangiogenic effects, making it a versatile and context-dependent player in kidney pathophysiology. Elevated circulating angiopoietin-2 levels in clinical scenarios are associated with sepsis and acute kidney injury (AKI), emphasizing its role as a biomarker of disease severity. In diabetic kidney disease, circulating angiopoietin-2 correlates with albuminuria, a crucial indicator of disease progression, and may serve as a treatment target in protecting the endothelium. Angiopoietin-2 is implicated in chronic kidney diseases (CKDs), where its elevated circulating levels correlate with kidney outcomes and cardiovascular complications, suggesting its potential impact on kidney function and overall health. In experimental settings, angiopoietin-2 plays a pivotal role in angiogenesis and lymphangiogenesis, influencing vascular stability and endothelial integrity. The context-dependent agonist and antagonist role of angiopoietin-2 is regulated by a Tie-2 phosphatase, vascular endothelial protein tyrosine phosphatase (VEPTP), further underscoring its complexity. Angiopoietin-2 is also involved in regulating cellular integrity, inflammation, and endothelial permeability, making it a promising therapeutic target for conditions characterized by disrupted endothelial junctions and vascular dysfunction. This review provides a comprehensive overview of the diverse roles of angiopoietin-2 in kidney research, offering insights into potential therapeutic targets and advancements in managing kidney diseases.