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J Cell Mol Med. 2017 Dec;21(12):3633-3640. doi: 10.1111/jcmm.13274. Epub 2017 Jul 17.

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

Hong H1,2, Chen F1, Qiao Y3, Yan Y2,4, Zhang R2, Zhu Z5, Li H1,6, Fan Y2, Xu G1.

Author information

1
Department of Otolaryngology and Head Neck Surgery of the First Hospital Affiliated with Sun Yat-sen University, Guangzhou, Guangdong, China.
2
Department of Otolaryngology and Head Neck Surgery of the Fifth Hospital Affiliated with Sun Yat-sen University, Zhuhai, Guangdong, China.
3
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore.
4
Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore.
5
Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
6
Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.

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.

KEYWORDS:

GSK-3β; chronic rhinosinusitis without nasal polyps; nuclear factor-κB; phosphorylation

PMID:
28714566
PMCID:
PMC5706567
DOI:
10.1111/jcmm.13274
[Indexed for MEDLINE]
Free PMC Article

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