摘要
Netrin-1,an axon guidance factor,and its receptor UNC5B play important roles in axonal development and angiogenesis.This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis.Netrin-1 and UNC5B were upregulated in streptozotocininduced DKD Wistar rats,and their expression was compared with that in healthy controls.However,exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis.This effect was likely associated with SRC pathway deactivation.Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs.These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD.Therefore,introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.
基金
This study was supported by the National Key R&D Program of China(No.2016YFC1305500)
the National Natural Science Foundation of China(Nos.81770725,61671479,and 61971441).