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Gene regulation by glucocorticoid in ENaC-mediated Na(+) transport by middle ear epithelial cells.

Authors
 Bo G. Kim  ;  Jin Y. Kim  ;  Minbum Kim  ;  Chang-Hoon Kim  ;  Jae Y. Choi  ;  Sung H. Kim 
Citation
 Laryngoscope, Vol.124(2) : 27-33, 2014 
Journal Title
 Laryngoscope 
ISSN
 0023-852X 
Issue Date
2014
Abstract
OBJECTIVES/HYPOTHESIS: The epithelial sodium channel (ENaC) is a Na(+) transport channel located in the apical membrane of the human middle ear epithelium. Although ENaC-mediated sodium transport has been reported to be upregulated by dexamethasone in human middle ear epithelium, there has been no study of the downstream pathways for increased ENaC expression mediated by glucocorticoids in this tissue. We investigated the effect of dexamethasone on the expression of ENaC and glucocorticoid regulatory genes for ENaC expression in human middle ear epithelial cells (HMEECs). STUDY DESIGN: In vitro investigation. METHODS: Real-time RT-PCR and Western blot analysis were used to determine the expression level of ENaC and its regulatory genes in HMEECs. RESULTS: The transcript and protein expression of the α-, β-, and γ-ENaC subunits were all upregulated by dexamethasone (100 nM) in HMEECs. Dexamethasone treatment also increased the transcript expression of serum/glucocorticoid-regulated kinase1 (SGK1) and neural precursor cell-expressed developmentally downregulated (Nedd) 4-2, and decreased the transcript expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). ENaC transcript expression was not changed after mifepristone (a glucocorticoid antagonist, 100 nM) + dexamethasone treatment when compared to the control, but increased after spironolactone (a mineralocorticoid antagonist, 100 nM) + dexamethasone treatment. CONCLUSIONS: These findings indicate that dexamethasone increases the transcript and protein expression of the α-, β-, and γ-ENaC subunits via the GR-SGK1-Nedd4-2 pathway and provides insight into the molecular mechanism of the increased sodium transport mediated by ENaC with steroid treatment in HMEECs.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/lary.24397/abstract
DOI
10.1002/lary.24397
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Bo Gyung(김보경)
Kim, Sung Huhn(김성헌)
Kim, Jin Young(김진영)
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98067
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