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2020, Volume 14, Issue 3

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Frontiers of Medicine >> 2020, Volume 14, Issue 3 doi: 10.1007/s11684-019-0715-7

Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

. Department of Nephrology, Chinese People’s Liberation Army (PLA) General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing 100853, China.. Department of Nephrology, Henan Provincial Key Laboratory of Kidney Disease and Immunology, Henan Provincial People’s Hospital (Zhengzhou University People’s Hospital), Zhengzhou 450003, China

Accepted: 2019-12-25 Available online: 2019-12-25
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Abstract

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.

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