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Aldosterone-induced expression of ENaC-α is associated with activity of p65/p50 in renal epithelial cells

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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.

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The authors declare that they have no competing conflict of interests.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Authors and Affiliations

  1. Department of Nephrology, Wuxi No. 2 People’s Hospital, 68 Zhongshan Road, Wuxi, 214000, China

    Rongquan Chen, Wenjuan Sun, Hui Gu & Yun Cheng

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  1. Rongquan Chen
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  2. Wenjuan Sun
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  3. Hui Gu
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  4. Yun Cheng
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Correspondence to Yun Cheng.

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Chen, R., Sun, W., Gu, H. et al. Aldosterone-induced expression of ENaC-α is associated with activity of p65/p50 in renal epithelial cells. J Nephrol 30, 73–79 (2017). https://doi.org/10.1007/s40620-015-0231-z

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  • DOI: https://doi.org/10.1007/s40620-015-0231-z

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