Slit2-Robo signaling: a novel regulator of vascular injury

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.