Transcriptome analysis identifies DMRT3 in nasal polyp epithelial cells
of patients suffering from Nonsteroidal anti-inflammatory drugs-
Exacerbated Respiratory Disease (N-ERD)
Abstract
Background: N-ERD is a syndrome characterized by chronic rhinosinusitis
nasal polypsasthma and aspirin intolerance. An imbalance of eicosanoid
metabolism with overproduction of CysLTs has been associated with N-ERD
however, the precise mechanisms underlying N-ERD are unknown. Objective:
To establish the transcriptome of the nasal polyp airway epithelial
cells derived from N-ERD patients to uncover the gene expression
patterns during this disease. Methods: Nasal airway epithelial cells
were isolated from 12 N-ERD polyps and 9 N-ERD non polyp nasal mucosa as
controls from the same subjects. RNA was sequenced on the Illumina HiSeq
2500. Potential gene candidate DMRT3 was selected from the
differentially expressed genes for validation. Results: Comparative
transcriptome profiling of nasal epithelial cells was achieved in N-ERD.
18 genes had twofold mean regulation expression differences or greater.
5 genes were upregulated including DMRT3 and 12 genes were
down-regulated. Differentially regulated genes included inflammation,
defense and immunity. Significantly enriched pathways were metabolic
process and embryonic development. ELISA results of DMRT3 in N-ERD
patients was significantly upregulated when compared to controls (p=
0.03). IHC of N-ERD nasal polyps localised DMRT3 and was predominantly
released in the airway epithelia. These results corroborate with our
findings. Conclusion: Findings suggest that DMRT3 could be potentially
involved in nasal polyps development in N-ERD patients. Known functions
of DMRT3 include nucleic acid binding and highly expressed during
embryonic development. Several genes are downregulated, hinting
dedifferentiation phenomenon in N-ERD polyps. However, further studies
are required to confirm the exact mechanism of polyps formation in N-ERD
patients.