title: Aldosterone-induced expression of ENaC-α is associated with activity of p65/p50 in renal epithelial cells.
abstract: The amiloride-sensitive epithelial sodium channel (ENaC), located in the apical membrane in the cortical collecting duct of the kidney, mediates the fine-tuned regulation of external Na+balance. Expression of the alpha-subunit of ENaC (ENaC-α) is regulated by a number of factors in the lung, including transcription factor nuclear factor kappa B (NF-κB). In the present study, we examined the effect of IKKβ/p65/p50 on ENaC-α in a murine cortical collecting duct cell line that endogenously expresses ENaC, mpkCCDc14 (CCD) cells. Aldosterone exposure led to up-regulation of ENaC-α and IKKβ, and nuclear p65 and p50. Knockdown of IKKβ or p65 exhibited >60 % reduction of aldosterone-induced ENaC-α mRNA levels. Chromatin immunoprecipitation and electrophoretic mobility shift assays demonstrated a specific interaction between p65/p50 and ENaC-α gene promoter, which was further confirmed using luciferase reporter-gene vectors transiently transfected into CCD cells. Taken together these data support an important role for p65/p50 in the direct regulation of ENaC-α transcription and have important implications for understanding the role of NF-κB in the regulation of renal function.
authors.affiliation: Department of Nephrology, Wuxi No. 2 People's Hospital, 68 Zhongshan Road, Wuxi, 214000, China.
authors.forename: Rongquan
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Wuxi No. 2 People's Hospital, 68 Zhongshan Road, Wuxi, 214000, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Wuxi No. 2 People's Hospital, 68 Zhongshan Road, Wuxi, 214000, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Nephrology, Wuxi No. 2 People's Hospital, 68 Zhongshan Road, Wuxi, 214000, China. ycheng2345@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051550:I-kappa B Kinase / Q000502:physiology; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D051996:Transcription Factor RelA / Q000502:physiology*
chemical_list: D053503:Epithelial Sodium Channels; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D000450:Aldosterone; D051550:I-kappa B Kinase
keywords: Aldosterone; Epithelial sodium channel; Renal epithelial cells; p65/p50