NOX4-dependent regulation of ENaC in hypertension and diabetic kidney disease

被引:28
|
作者
Pavlov, Tengis S. [1 ,2 ]
Palygin, Oleg [1 ]
Isaeva, Elena [1 ]
Levchenko, Vladislav [1 ]
Khedr, Sherif [1 ,3 ]
Blass, Gregory [1 ,6 ]
Ilatovskaya, Daria, V [1 ,5 ]
Cowley, Allen W., Jr. [1 ]
Staruschenko, Alexander [1 ,4 ]
机构
[1] Med Coll Wisconsin, Dept Physiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA
[2] Henry Ford Hlth Syst, Div Hypertens & Vasc Res, Detroit, MI USA
[3] Ain Shams Univ, Fac Med, Dept Physiol, Cairo, Egypt
[4] Clement J Zablocki VA Med Ctr, Milwaukee, WI USA
[5] Med Univ South Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA
[6] Western Kentucky Univ, Dept Biol, Bowling Green, KY 42101 USA
来源
FASEB JOURNAL | 2020年 / 34卷 / 10期
关键词
chronic kidney disease; diabetic nephropathy; ENaC; H2O2; NOX4; salt-sensitive hypertension; SALT-INDUCED HYPERTENSION; COLLECTING DUCT CELLS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; NADPH OXIDASE; RENAL INJURY; PRESSURE NATRIURESIS; SODIUM DELIVERY; ROS PRODUCTION; NITRIC-OXIDE;
D O I
10.1096/fj.202000966RR
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
NADPH oxidase 4 (NOX4) is the most abundant NOX isoform in the kidney; however, its importance for renal function has only recently emerged. The NOX4-dependent pathway regulates many factors essential for proper sodium handling in the distal nephron. However, the functional significance of this pathway in the control of sodium reabsorption during the initiation of chronic kidney disease is not established. The goal of this study was to test Nox4-dependent ENaC regulation in two models: SS hypertension and STZ-induced type 1 diabetes. First, we showed that genetic ablation ofNox4in Dahl salt-sensitive (SS) rat attenuated a high-salt (HS)-induced increase in epithelial Na(+)channel (ENaC) activity in the cortical collecting duct. We also found that H(2)O(2)upregulated ENaC activity, and H(2)O(2)production was reduced in both the renal cortex and medulla in SS(Nox4-/-)rats fed an HS diet. Second, in the streptozotocin model of hyperglycemia-induced renal injury ENaC activity in hyperglycemic animals was elevated in SS but not SS(Nox4-/-)rats. NaCl cotransporter (NCC) expression was increased compared to healthy controls, while expression values between SS and SS(Nox4-/-)groups were similar. These data emphasize a critical contribution of the NOX4-mediated pathway in maladaptive upregulation of ENaC-mediated sodium reabsorption in the distal nephron in the conditions of HS- and hyperglycemia-induced kidney injury.
引用
收藏
页码:13396 / 13408
页数:13
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