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Gene regulation by glucocorticoid in ENaC-mediated Na⁺ transport by middle ear epithelial cells.
Laryngoscope. 2014 Feb; 124(2):E27-33.L

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.

LEVEL OF EVIDENCE

N/A.

Authors+Show Affiliations

Department of Otorhinolaryngology, Yonsei University, College of Medicine, Seoul.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24114932

Citation

Kim, Bo G., et al. "Gene Regulation By Glucocorticoid in ENaC-mediated Na⁺ Transport By Middle Ear Epithelial Cells." The Laryngoscope, vol. 124, no. 2, 2014, pp. E27-33.
Kim BG, Kim JY, Kim M, et al. Gene regulation by glucocorticoid in ENaC-mediated Na⁺ transport by middle ear epithelial cells. Laryngoscope. 2014;124(2):E27-33.
Kim, B. G., Kim, J. Y., Kim, M., Kim, C. H., Choi, J. Y., & Kim, S. H. (2014). Gene regulation by glucocorticoid in ENaC-mediated Na⁺ transport by middle ear epithelial cells. The Laryngoscope, 124(2), E27-33. https://doi.org/10.1002/lary.24397
Kim BG, et al. Gene Regulation By Glucocorticoid in ENaC-mediated Na⁺ Transport By Middle Ear Epithelial Cells. Laryngoscope. 2014;124(2):E27-33. PubMed PMID: 24114932.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gene regulation by glucocorticoid in ENaC-mediated Na⁺ transport by middle ear epithelial cells. AU - Kim,Bo G, AU - Kim,Jin Y, AU - Kim,Minbum, AU - Kim,Chang-Hoon, AU - Choi,Jae Y, AU - Kim,Sung H, Y1 - 2013/10/16/ PY - 2013/04/09/received PY - 2013/08/02/revised PY - 2013/08/19/accepted PY - 2013/10/12/entrez PY - 2013/10/12/pubmed PY - 2014/3/19/medline KW - ENaC KW - HMEECs KW - Human middle ear epithelial cells KW - dexamethasone SP - E27 EP - 33 JF - The Laryngoscope JO - Laryngoscope VL - 124 IS - 2 N2 - 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. LEVEL OF EVIDENCE: N/A. SN - 1531-4995 UR - https://www.unboundmedicine.com/medline/citation/24114932/Gene_regulation_by_glucocorticoid_in_ENaC_mediated_Na⁺_transport_by_middle_ear_epithelial_cells_ L2 - https://doi.org/10.1002/lary.24397 DB - PRIME DP - Unbound Medicine ER -