Multiple gene expression profiling suggests epithelial dysfunction in polypoid chronic rhinosinusitis

Abstract

SUMMARY Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disorder resulting from a complex gene-environment interaction. Although its aetiology remains elusive, numerous studies reported gene expression alterations of factors apparently implicated in all aspects of the inflammatory response. However, most investigations are limited, unconfirmed analyses of a single gene. Moreover, studies concerning multiple gene expression analyses, usually on inflammatory mediators (e.g. cytokines), show contrasting outcomes in part due to use of heterogeneous samples or methodologies with limited power. In this scenario, our goal was to simultaneously evaluate the expression of a panel of selected genes ( AQP5 , MUC5AC , CAV1 , LTF, COX2 , PGDS, TNF α, TGF β 1, MGB1 ) potentially involved in CRS inflammatory mechanisms. While most of the samples collected were excluded from the analysis because of poor quality RNA, we were able to demonstrate statistically significant downregulation of the AQP5, CAV1, LTF, MGB1 genes in a specific subset of polypoid CRS (patients without typical comorbidities), which might suggest relevant underlying epithelial dysfunction. Further studies are needed to enrich our knowledge on the pathogenesis of CRS. Forthcoming approaches might utilise next-generation RNA sequencing and comprehensive bioinformatics analyses to better characterise the transcriptome profiles of CRS endotypes.

Exploring the role of nasal cytology in chronic rhinosinusitis

“…This aspect is the inspiring concept underlying the recent "reboot approach" 24 . Moreover, this region, in addition to a different embryological origin, shows a morpho-histological structure that is not identical to that of the middle meatus 22,25 . She et al demonstrated that 66% of CRS patients with CRS show marked inflammation in the inferior turbinate, but that the inflammation is much more intense in maxillary sinus mucosa 20 .…”

“…This aspect is the inspiring concept underlying the recent “reboot approach” 24 . Moreover, this region, in addition to a different embryological origin, shows a morpho-histological structure that is not identical to that of the middle meatus 22 , 25 .…”

“…To make matters complicated, She et al demonstrated a lack of significant correlation between the total and individual inflammatory cell counts in inferior turbinate versus paranasal sinus mucosa, questioning the diagnostic value of nasal cytology for CRS 20 . If it is true that the term CRS has been coined precisely to express that every sinus inflammation translates contextually into an inflammation of the nasal mucosa (and therefore also of the inferior turbinate) and that transcriptomic studies showed a substantially overlapping gene expression profile of various nasal subsites 21 , 22 , it is also true that clinical practice teaches that the phenotypic manifestations of CRS usually spare the mucosa of the inferior turbinates 23 . This aspect is the inspiring concept underlying the recent “reboot approach” 24 .…”

Expression, Distribution and Role of Aquaporins in Various Rhinologic Conditions

“…Thus, the authors suggested that the mucosal epithelial barrier is compromised in the context of CRS disease, especially CRSwNP, and that loss of AQP5, which might act as a tight junction protein, plays a role in the development of mucosal edema and the pathophysiology of nasal polyp formation [ 57 ]. Another study comparing normal control and CRSwNP tissue also reported a decrease in AQP5 in tissues from CRSwNP patients [ 58 ]. The authors of this study concluded that loss of AQP5 caused impaired tight junction regulation of water transport and cell volume and failure to maintain epithelial water homeostasis, resulting in edema and polyp formation and production of thick secretions—typical features of CRSwNP.…”

Structural changes in the extracellular matrix after cross-linking of nasal polyp tissue

“…Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterised by chronic inflammation of the nasal mucosa with an altered remodelling process, which affects extracellular matrix (ECM) formation and facilitates mechanical dysfunction and oedema formation 1 . The pathogenesis of CRSwNP is still not fully understood 2,3 ; however, its foundation is the aforementioned chronic inflammatory process, characterised by a major imbalance in immunomodulation which increases inflammatory cells (such as dendritic cells, eosinophils, and T helper cells) and decreases immunoregulatory cells (such as regulatory T cells), as well as an impaired immunomodulation of mesenchymal stem cells 4,5 . Studies on the mechanical forces involved in nasal polyp development have been conducted in an attempt to at least partly elucidate the pathophysiology of CRSwNP 1,6,7 .…”