Small GTPase Arf6 regulates diabetes-induced cholesterol accumulation in podocytes
Small GTPase Arf6 regulates diabetes-induced cholesterol accumulation in podocytes
复制标题
小 GTP 酶 Arf6 调节糖尿病诱导的足细胞胆固醇积累
DOI：
10.1002/jcp.28924
复制
发表时间：
2019-12-01
影响因子：
5.6
通讯作者：
Ding, Guohua
中科院分区：
文献类型：
--
作者：
Hu, Jijia;Yang, Qian;Ding, Guohua
Podocyte injury is a critical factor for the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanisms of podocyte injury in DKD have not been completely elucidated. Studies suggested that intracellular cholesterol accumulation was correlated with podocyte injury, but the cause of podocyte cholesterol disorders in DKD are still unknown. ADP-ribosylation factor 6 (Arf6) is a small GTPase with pleiotropic effects and has previously been shown to regulate ATP-binding cassette transporter 1 (ABCA1) recycling, and thus, cholesterol homeostasis. However, Arf6 involvement in cholesterol metabolism in podocytes is scarce. To investigate the role of Arf6 in cholesterol modulation in podocytes, the effect of Arf6 on the regulation of the cholesterol transporter ABCA1 was studied in podocytes in vivo and in vitro. Intracellular cholesterol accumulation was significantly increased in podocytes from streptozotocin-induced diabetic rats and that hyperglycemia downregulated the expression of Arf6. Arf6 knockdown could cause ABCA1 recycling disorders, and thus, further aggravate cholesterol accumulation in podocytes under high-glucose (HG) conditions. Our results demonstrate that HG-induced cholesterol accumulation and cellular injury in podocytes may be related to the recycling disorder of ABCA1 caused by the downexpression of Arf6 in DKD.
