Abstract
The decrease of peritubular capillaries, a pathological feature of acute kidney injury (AKI), is a critical part that promotes the transition of AKI to chronic kidney disease (CKD). Ginsenoside Rb1 (Rb1) has various pharmacological effects on multiple systemic diseases. However, whether Rb1 delays the transition of AKI to CKD and the mechanism are unclear. Here, we discovered that Rb1 could alleviate kidney pathological damage in mice with unilateral ischaemia/reperfusion injury (uIRI), and it enhanced kidney function, reduced renal fibrosis while increasing microvessel density. By virtual screening and molecular docking approaches, we identified vascular endothelial growth factor receptor 2 (VEGFR2) as the principal molecular target of Rb1. Furthermore, we uncovered that Rb1 activated AKT phosphorylation-mediated angiogenesis through binding to VEGFR2, which promoted endothelial tube formation and nitric oxide (NO) release in human umbilical vein endothelial cells (HUVECs) and then relieved the endothelial dysfunction induced by hypoxia-reoxygenation (H/R). Also, we found that Rb1 activated VEGFR2/AKT signalling in the kidney tissue of uIRI mice. Knocking down VEGFR2 or inhibiting the AKT signalling pathway can impair the proangiogenic effect of Rb1. Taken together, we demonstrated that Rb1 facilitated renal angiogenesis by activating the VEGFR2/AKT pathway of endothelial cells, thereby arresting the transition from AKI to CKD, and providing a potential therapeutic strategy for AKI.