Age-Related Increase of Collagen/Fibrin Deposition and High PAI-1 Production in Human Nasal Polyps

Abstract

Objective: Our previous studies showed an age-related increased prevalence of nasal polyps (NP) and reduced production of S100A8/9 in elderly patients with chronic rhinosinusitis with NP (CRSwNP). In this study, we investigated an unbiased age-related gene expression profile in CRSwNP subjects and healthy controls, and further identified the differences in their tissue remodeling.Methods: Microarrays using NP and uncinate tissues from health controls (elderly, age ≥65 vs. non-elderly, age 18–49) were performed, and differentially regulated genes were analyzed. Quantitative real-time PCR (qPCR), Immunostaining, Periodic acid-Schiff (PAS), trichrome staining, Western blot, and ELISA were performed for further investigation.Results: Microarrays identified differentially expressed genes according to disease and age; 278 in NP vs. controls, 75 in non-elderly NP vs. non-elderly controls, and 32 in elderly NP vs. elderly controls. qPCR confirmed that the PLAT gene was downregulated and the SERPINB2 gene upregulated in NP vs. controls. The serous glandular cell-derived antimicrobial protein/peptide-related genes such as BPIFB3, BPIFB2, LPO, and MUC7 were remarkably reduced in NP, regardless of age. SERPINE1 gene (plasminogen activator inhibitor-1, PAI-1) expression was significantly increased in elderly NP versus elderly controls. IHC and western blot confirmed significantly decreased production of MUC7 and LPO in NP versus controls. There was a trend of age-related reduction of submucosal gland cells in normal controls. Trichrome and immunofluorescence staining demonstrated an age-related increase of collagen and fibrin deposition in NP, consistent with increased PAI-1 production.Conclusion: This study demonstrated age-related differential glandular remodeling patterns and fibrosis in NP and normal controls. PAI-1 expression was significantly increased in elderly NP versus elderly controls, suggesting PAI-1 as a potential treatment target in elderly NP.

Increased SERPINB2 potentiates 15LO1 expression via STAT6 signalling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps

“…44 However, data supporting the association of T2 inflammation to SERPINB2 in CRSwNP are more limited, with a previous microarray study reporting increased SERPINB2 RNA expression in nasal polyp tissues as compared with HCs. 19 In the current study, we showed that SERPINB2 mRNA and protein were significantly increased in NPs from CRSwNP subjects as compared with HCs. A recent lower airway single-cell RNA sequencing study of asthma showed that SERPINB2 is one of the core genes which upregulated in all subtypes of bronchial epithelial cells.…”

“…SERPINB2, which is upregulated in asthma and associated with type-2 inflammation and asthma severity, is crucial for collagen fibrin deposition under epithelial layer in the airways. 19 In this study, we expand the disease implications of SERPINB2…”

“…17,18 The microarray analysis showed that the SERPINB2 gene was upregulated in NP tissues. 19 However, the pathophysiological function of inflammation associated with SERPINB2 and its role in CRSwNP, thus, remain unclear.…”

An emerging view on vascular fibrosis molecular mediators and relevant disorders: from bench to bed

“…Age as well as gender may additionally impact collagen deposition in different tissues. Increased collagen and fibrin deposition occurred in elderly normal controls when compared to non-elderly controls, and this was even more pronounced in elderly patients with nasal polyps (146), which was further confirmed by studying model organisms such as mice and C. elegans (147). The deposition of collagen fibers after surgery is significantly reduced in older men but not in women (148).…”

Bulk and single‐cell transcriptome sequencing reveal the metabolic feature in chronic rhinosinusitis with polyps

“…Subsequent subset analysis revealed enhanced glycolytic and hypoxia metabolism in subsets 1 and 6, predominantly present in nasal polyp tissues and exhibiting high expression of genes associated with collagen synthesis, particularly the collagenrelated gene P4HA1 (Figure 1D). Notably, studies have indicated a significant increase in collagen fibres in nasal polyps, 6 which may offer novel insights into the pathogenesis and treatment of CRSwNP.…”