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Current Pharmaceutical Biotechnology

Author(s): Xubo Chen, Qi Zhang, Chunping Yang, Yuehui Liu and Lihua Li*

DOI: 10.2174/1389201021666201008163534

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GRβ Regulates Glucocorticoid Resistance in Sudden Sensorineural Hearing Loss

Page: [1206 - 1215] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Background: In recent years, the incidence of sudden deafness has gradually increased, with a very limited understanding of its etiology and pathogenesis. Glucocorticoids are the first choice of the treatment, but some hormone-resistant patients are not sensitive to glucocorticoid therapy. The pathogenesis is not yet known. In this study, we aim to construct the HEI-OC1 cell line stably overexpressing Glucocorticoid Receptor Beta (GRβ), and identify its exact role in the cases of glucocorticoidresistant sudden deafness.

Methods: We used the endotoxin lipopolysaccharide-stimulated cochlear hair cells (HEI-OC1) to investigate the relationship of inflammation factor IL-2, TNF alpha, and SRp30c with the high expression GRβ. We built a stable GRβ high expression HEI-OC1 cell line and clarified its effects on the therapeutic effect of dexamethasone. MTT assay, colony formation assay, CCK-8 assay, Western blot, and RT-qPCR were utilized for characterizations.

Results: Dexamethasone reduced the LPS-induced inflammatory response from HEI-OC1 cells (p<0.05), detected by MTT assay. Dexamethasone could protect HEI-OC1 cells, but its protective effect was weakened due to the transfection of SRp30c over-expression plasmid (p<0.05). The transfection of SRp30c over-expression plasmid in HEI-OC1 cells could elevate the expressions of GRβ (p<0.05).

Conclusion: We clarified the mechanisms of high expression of GRβ in glucocorticoid-resistant sudden sensorineural hearing loss, and proved that the inhibition of SRp30c may act as a new treatment way of glucocorticoid-resistant sudden sensorineural hearing loss.

Keywords: Glucocorticoid resistance, dexamethasone, sudden sensorineural hearing loss, GRβ, SRp30c, LPS.

Graphical Abstract

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