Administration of Slit2 analogs to minimize vascular injuries, inflammation, and kidney involvement in β-thalassemia: A hypothesis

Abstract

Patients with β-thalassemia experience various complications, including vascular damage, inflammation, and kidney dysfunction. Although antiplatelet and chelation therapies help reduce these complications, more targeted treatment is needed to enhance therapeutic efficacy and improve patient prognosis. Slit homolog 2 (Slit2) is a secreted extracellular matrix glycoprotein. Upon binding to their cognate roundabout (Robo) receptors expressed on platelets, leukocytes, and endothelial cells, Slit2-Robo complexes activate multiple downstream signaling pathways. Accumulating evidence suggests that Slit2-Robo signaling inhibits platelet adhesion and spreading. Slit2-Robo signaling decreases leukocyte migration and proinflammatory cytokine release and can be modulated by Slit2 analogs. Therefore, we hypothesized that the administration of Slit2 might help minimize vascular injury, inflammation, and kidney dysfunction-related complications in patients with β-thalassemia. Our proposed idea provides a deeper understanding of the pathophysiology of β-thalassemia, and modulation of the Slit2-Robo signaling cascade could serve as an alternative therapy in the future, pending validation.