GSK-3β activation index is a potential indicator for recurrent inflammation of chronic rhinosinusitis without nasal polyps.

Abstract

Chronic rhinosinusitis without nasal polyps (CRSsNP) is one of the most common otorhinolaryngologic diseases worldwide. However, the underlying mechanism remains unclear. In this study, the expression of glycogen synthase kinase 3 (GSK-3) was quantitatively evaluated in patients with CRSsNP (n = 20) and healthy controls (n = 20). The mRNA levels of GSK-3α and GSK-3β were examined by qPCR, the immunoreactivities of GSK-3β and nuclear factor-κB (NF-κB) were examined by immunohistochemistry (IHC) staining, and the protein levels of GSK-3β, phospho-GSK-3β (p-GSK-3β, s9) and NF-κB were examined using Western blot analysis. We found that GSK-3 was highly expressed in both CRSsNP and control groups without significant difference in both GSK-3β mRNA and protein levels. However, when compared with healthy control group, the GSK-3β activation index, defined as the ratio of GSK-3β over p-GSK-3β, was significantly decreased, whereas the NF-κB protein abundance was significantly increased in CRSsNP group (P < 0.05). Strikingly, the GSK-3β activation index, was highly correlated with NF-κB protein level, as well as CT scores in CRSsNP group (P < 0.05). It was also highly correlated with the mRNA expressions of inflammation-related genes, including T-bet, IFN-γ and IL-4 in CRSsNP group (P < 0.05). Our findings suggest that GSK-3β activation index, reflecting the inhibitory levels of GSK-3β through phosphorylation, may be a potential indicator for recurrent inflammation of CRSsNP, and that the insufficient inhibitory phosphorylation of GSK-3β may play a pivotal role in the pathogenesis of CRSsNP.

• Authors: Haiyu Hong, Fenghong Chen, Yongkang Qiao, Yan Yan, Rongkai Zhang, Zhe Zhu, Huabin Li, Yunping Fan, Geng Xu
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 21 Issue 12 Pg. 3633-3640 (Dec 2017) ISSN: 1582-4934 [Electronic] England
• PMID: 28714566 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Biomarkers
• IFNG protein, human
• IL4 protein, human
• NF-kappa B
• RNA, Messenger
• T-Box Domain Proteins
• T-box transcription factor TBX21
• Interleukin-4
• Interferon-gamma
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3
• glycogen synthase kinase 3 alpha

Topics

• Adolescent
• Adult
• Biomarkers (metabolism)
• Case-Control Studies
• Chronic Disease
• Female
• Gene Expression Regulation
• Glycogen Synthase Kinase 3 (genetics, immunology)
• Glycogen Synthase Kinase 3 beta (genetics, immunology)
• Humans
• Inflammation
• Interferon-gamma (genetics, immunology)
• Interleukin-4 (genetics, immunology)
• Male
• Middle Aged
• NF-kappa B (genetics, immunology)
• Nasal Polyps
• Phosphorylation
• RNA, Messenger (genetics, immunology)
• Recurrence
• Rhinitis (diagnosis, genetics, metabolism, physiopathology)
• Signal Transduction
• Sinusitis (diagnosis, genetics, metabolism, physiopathology)
• T-Box Domain Proteins (genetics, immunology)