Targeting angiogenesis and lymphangiogenesis in kidney disease

• Published in: Nature reviews. Nephrology Vol. 16; no. 5; pp. 289 - 303
• Main Authors: Tanabe, Katsuyuki, Wada, Jun, Sato, Yasufumi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2020; Nature Publishing Group
• Subjects: 631/250/1617/290; 631/443/592/16; 692/4022/1585; Angiogenesis; Antigens; Cancer; Care and treatment; Cell growth; Development and progression; Diabetes; Edema; Genetic aspects; Growth factors; Health aspects; Humans; Kidney diseases; Kinases; Lymphangiogenesis; Medicine; Medicine & Public Health; Neovascularization; Neovascularization, Pathologic - etiology; Neovascularization, Pathologic - therapy; Nephrology; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - pathology; Renal Insufficiency, Chronic - therapy; Review Article; Roles; Vascular endothelial growth factor; Veins & arteries; Japan
• ISSN: 1759-5061; 1759-507X
• DOI: 10.1038/s41581-020-0260-2

The kidney is permeated by a highly complex vascular system with glomerular and peritubular capillary networks that are essential for maintaining the normal functions of glomerular and tubular epithelial cells. The integrity of the renal vascular network depends on a balance of proangiogenic and antiangiogenic factors, and disruption of this balance has been identified in various kidney diseases. Decreased levels of the predominant proangiogenic factor, vascular endothelial growth factor A (VEGFA), can result in glomerular microangiopathy and contribute to the onset of preeclampsia, whereas upregulation of VEGFA has roles in diabetic kidney disease (DKD) and polycystic kidney disease (PKD). Other factors that regulate angiogenesis, such as angiopoietin 1 and vasohibin 1, have been shown to be protective in animal models of DKD and renal fibrosis. The renal lymphatic system is important for fluid homeostasis in the kidney, as well as the transport of immune cells and antigens. Experimental studies suggest that the lymphangiogenic factor VEGFC might have protective effects in PKD, DKD and renal fibrosis. Understanding the physiological and pathological roles of factors that regulate angiogenesis and lymphangiogenesis in the kidney has led to the development of novel therapeutic strategies for kidney diseases. In this Review, the authors discuss current understanding of the expression and dysregulation of factors that regulate angiogenesis and lymphangiogenesis in the kidney, as well as potential therapeutic strategies to target these factors during various kidney diseases. Key points In the kidney, the glomerular and peritubular capillary networks are critical for normal nephron function; disruption of these networks can lead to the development and progression of various kidney diseases. Normal expression of the proangiogenic factor vascular endothelial growth factor A (VEGFA), the vascular maturation factor angiopoietin 1 and the antiangiogenic factor vasohibin 1 is essential for maintaining capillary networks in the kidney. The expression of proangiogenic and antiangiogenic factors can be altered in kidney diseases, including diabetic kidney disease (DKD) and renal fibrosis; targeting these factors is considered a promising therapeutic strategy. Formation of abnormal lymphatic vessel networks accompanied by inflammatory infiltration is associated with various kidney diseases. Experimental studies suggest that administration of VEGFC — the main regulator of lymphangiogenesis — might be beneficial in DKD, renal fibrosis and polycystic kidney disease. Novel approaches to selectively delivering angiogenesis-regulating factors to the placenta and kidney have been developed as therapeutic strategies for preeclampsia and renovascular disease, respectively.