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

doi:10.1007/s11684-019-0715-7

Frontiers of Medicine

2020, Vol. 14

Issue (3): 293-304 https://doi.org/10.1007/s11684-019-0715-7

本期目录

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

Xiaojing Jiao^1,², Dong Zhang¹, Quan Hong¹, Lei Yan², Qiuxia Han¹, Fengmin Shao²(

), Guangyan Cai¹, Xiangmei Chen¹, Hanyu Zhu¹(

)

¹. 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
². 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

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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.

Key words： netrin-1 VEGF-165 UNC5B angiogenesis diabetic kidney disease

收稿日期: 2019-01-01 出版日期: 2020-06-08

Corresponding Author(s): Fengmin Shao,Hanyu Zhu

引用本文:

. [J]. Frontiers of Medicine, 2020, 14(3): 293-304.
Xiaojing Jiao, Dong Zhang, Quan Hong, Lei Yan, Qiuxia Han, Fengmin Shao, Guangyan Cai, Xiangmei Chen, Hanyu Zhu. Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease. Front. Med., 2020, 14(3): 293-304.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-019-0715-7
https://academic.hep.com.cn/fmd/CN/Y2020/V14/I3/293

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