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Transcriptome analysis identifies DMRT3 in nasal polyp epithelial cells of patients suffering from Nonsteroidal anti-inflammatory drugs- Exacerbated Respiratory Disease (N-ERD)
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  • VS Priyadharshini,
  • Alejandro Jiménez-Chobillon,
  • Jos de Graaf,
  • Raul Gutiérrez de Velasco,
  • Christina Gratziou,
  • Fernando Ramirez-Jimenez,
  • Luis Teran
VS Priyadharshini
Instituto Nacional de Enfermedades Respiratorias
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Alejandro Jiménez-Chobillon
Instituto Nacional de Enfermedades Respiratorias
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Jos de Graaf
Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz gGmbH (TRON)
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Raul Gutiérrez de Velasco
Instituto Nacional de Enfermedades Respiratorias
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Christina Gratziou
Evgenidio Hospital
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Fernando Ramirez-Jimenez
Instituto Nacional de Enfermedades Respiratorias
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Luis Teran
Instituto Nacional de Enfermedades Respiratorias
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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.