Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Curr Opin Nephrol Hypertens. 2013 Jul;22(4):445-51. doi: 10.1097/MNH.0b013e32836235f4.
Vascular injury is a common contributor to, and complication of, kidney disease. Given the prevalence and importance of vascular injury in renal disease, interest has grown in a novel signaling pathway first identified in developing neurons that also has widespread effects on vascular structure and function, comprising the secreted ligand Slit2 and its cognate Roundabout (Robo) receptors.
Although initially discovered as a modulator of neuronal migration during development, the Slit2-Robo signaling pathway has recently been found to regulate the structure and function of various subsets of vascular cells and circulating hematopoietic cells that interact with the vessel wall. Through the regulation of intermediate signaling enzymes that control the organization of the actin cytoskeleton, Slit2 and its Robo receptors regulate such diverse processes as angiogenesis, endothelial permeability, vascular smooth muscle cell migration, and thrombosis.
Recent advances in our understanding of Slit2-Robo signaling have provided novel insights into the pathophysiology of vascular injury that is commonly associated with renal disease. These insights have created potential opportunities for the development of new therapies targeting vascular injury associated with renal disease.
血管损伤是肾脏疾病的常见病因和并发症。鉴于血管损伤在肾脏疾病中的普遍性和重要性，人们对一种新的信号通路产生了兴趣，该通路最初在发育中的神经元中被发现，对血管结构和功能也有广泛的影响，包括分泌配体 Slit2 和其同源的 Roundabout（Robo）受体。
尽管最初被发现是发育过程中神经元迁移的调节剂，但 Slit2-Robo 信号通路最近被发现调节与血管壁相互作用的各种血管细胞和循环造血细胞的结构和功能。Slit2 和其 Robo 受体通过调节控制肌动蛋白细胞骨架组织的中间信号酶，调节血管生成、内皮通透性、血管平滑肌细胞迁移和血栓形成等多种过程。
我们对 Slit2-Robo 信号的理解的最新进展为与肾脏疾病相关的血管损伤的病理生理学提供了新的见解。这些见解为开发针对肾脏疾病相关血管损伤的新疗法创造了潜在的机会。
