Luo An-Jie, Chang Fan-Chi, Lin Shuei-Liong
Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Renal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Kidney Int Rep. 2024 Sep 6;9(12):3375-3385. doi: 10.1016/j.ekir.2024.09.001. eCollection 2024 Dec.
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.
血管生成素-2是血管生成和血管重塑的重要促成因素，在肾脏研究中越来越受到认可。本文综述探讨了血管生成素-2在肾脏疾病中的临床见解和实验前景。传统上，血管生成素-2被视为Tie-2的拮抗剂，Tie-2是内皮细胞和一些造血干细胞的受体酪氨酸激酶，血管生成素-2具有促血管生成和抗血管生成作用，使其在肾脏病理生理学中成为一个多功能且依赖于环境的参与者。临床情况下循环血管生成素-2水平升高与脓毒症和急性肾损伤（AKI）相关，强调了其作为疾病严重程度生物标志物的作用。在糖尿病肾病中，循环血管生成素-2与蛋白尿相关，蛋白尿是疾病进展的关键指标，并且可能作为保护内皮的治疗靶点。血管生成素-2与慢性肾脏病（CKD）有关，其循环水平升高与肾脏预后和心血管并发症相关，表明其对肾功能和整体健康的潜在影响。在实验环境中，血管生成素-2在血管生成和淋巴管生成中起关键作用，影响血管稳定性和内皮完整性。血管生成素-2的环境依赖性激动剂和拮抗剂作用由Tie-2磷酸酶——血管内皮蛋白酪氨酸磷酸酶（VEPTP）调节，进一步强调了其复杂性。血管生成素-2还参与调节细胞完整性、炎症和内皮通透性，使其成为以内皮连接破坏和血管功能障碍为特征的疾病的有前景的治疗靶点。本文综述全面概述了血管生成素-2在肾脏研究中的多种作用，为潜在治疗靶点和肾脏疾病管理进展提供了见解。
