Asymmetric expression level of clock genes in left vs. right nasal mucosa in humans with and without allergies and in rats: Circadian characteristics and possible contribution to nasal cycle.

Ha Kyun Kim,Tae Hoon Kim,Jae Hyung Kim,Hyun Jung Kim,Sang Hag Lee,Henrik Oster

doi:10.1371/journal.pone.0194018

Abstract

Numerous peripheral tissues possess self-sustaining daily biologic rhythms that are regulated at the molecular level by clock genes such as PER1, PER2, CLOCK, and BMAL1. Physiological function of nasal mucosa exhibits rhythmic variability to a day-night environmental cycle. Nevertheless, little is known of the expression and distribution pattern of clock genes in nasal mucosa. The present study investigates the expression level and distribution pattern of PER1, PER2, CLOCK, and BMAL1 genes in nasal mucosa of healthy controls, allergic rhinitis patients, and normal rats. In human and rat nasal mucosa, the levels of these genes are asymmetrically expressed in nasal mucosa derived from right and left cavities in normal controls, allergic patients, and rat. In human nasal mucosa, the expression levels of these genes were higher in the decongested side than the congested mucosa. In rat nasal mucosa, these clock genes are expressed in a rhythmic circadian manner under the regular light/dark cycles. The expression levels of MUC5AC, a key mucin genes produced in superficial epithelium, are higher in decongested side than that congested side in human nasal mucosa. In rat nasal mucosa, MUC5AC levels showed a circadian rhythm which was associated with different expression levels in nasal mucosa derived from the right and left nasal cavities. Taken together with these results, the present study shows that the clock genes such as PER1, PER2, CLOCK, and BMAL1 are present in human and rat nasal mucosa, and suggest that these clock genes may control the pathophysiological function of nasal mucosa as circadian oscillators and affect the maintenance of the nasal cycle.

Highlights

Spontaneous periodic changes in the congestion state of the nasal mucosa associated with reciprocal fluctuations in nasal resistance to airflow are referred to as the nasal cycle
These results revealed that these genes had asymmetric expression levels in nasal mucosa from both turbinates in normal control and allergic patients and showed that the expression levels of these genes were higher in decongested mucosa than congested mucosa, irrespective of GAPDH or EEF1A1 usage as housekeeping gene (Fig 1D and 1E)
PER1, PER2, CLOCK, and BMAL1 were asymmetrically expressed in nasal mucosa derived from the right and left nasal cavities of normal control and allergic patients

Summary

Introduction

Spontaneous periodic changes in the congestion state of the nasal mucosa associated with reciprocal fluctuations in nasal resistance to airflow are referred to as the nasal cycle. Cyclical shrinkage and dilation of the venous sinusoids distributed in the nasal mucosa contributes to the spontaneous alteration in nasal airflow [1,2,3,4,5]. This physiological phenomenon is present in 80% of normal human subjects and is found in several animal species [5,6,7,8,9]. The hypothalamus participates in regulation of the nasal cycle via the sympathetic nervous system distributed in the nasal mucosa [15]

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Conclusion