Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease
Xiaojing Jiao , Dong Zhang , Quan Hong , Lei Yan , Qiuxia Han , Fengmin Shao , Guangyan Cai , Xiangmei Chen , Hanyu Zhu
Front. Med. ›› 2020, Vol. 14 ›› Issue (3) : 293 -304.
Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease
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 streptozotocin-induced 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.
netrin-1 / VEGF-165 / UNC5B / angiogenesis / diabetic kidney disease
Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature
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