Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Severe Type 2 Inflammation Leads to High PAF-Associated Pathology in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP): Hierarchal Cluster Analysis Using Bulk RNA Barcoding and Sequencing

Takashi Ishino
ORCID logo ,
Takashi Oda
,
Tomohiro Kawasumi
,
Kota Takemoto
ORCID logo ,
Manabu Nishida
,
Yuichiro Horibe
,
Nobuyuki Chikuie
,
Takayuki Taruya
,
Takao Hamamoto
ORCID logo ,
Tsutomu Ueda
,
Sachio Takeno
* ORCID logo
Version 1 : Received: 3 January 2024 / Approved: 17 January 2024 / Online: 17 January 2024 (13:57:17 CET)

A peer-reviewed article of this Preprint also exists.

Ishino, T.; Oda, T.; Kawasumi, T.; Takemoto, K.; Nishida, M.; Horibe, Y.; Chikuie, N.; Taruya, T.; Hamamoto, T.; Ueda, T.; Takeno, S. Severe Type 2 Inflammation Leads to High Platelet-Activating-Factor-Associated Pathology in Chronic Rhinosinusitis with Nasal Polyps—A Hierarchical Cluster Analysis Using Bulk RNA Barcoding and Sequencing. Int. J. Mol. Sci. 2024, 25, 2113. Ishino, T.; Oda, T.; Kawasumi, T.; Takemoto, K.; Nishida, M.; Horibe, Y.; Chikuie, N.; Taruya, T.; Hamamoto, T.; Ueda, T.; Takeno, S. Severe Type 2 Inflammation Leads to High Platelet-Activating-Factor-Associated Pathology in Chronic Rhinosinusitis with Nasal Polyps—A Hierarchical Cluster Analysis Using Bulk RNA Barcoding and Sequencing. Int. J. Mol. Sci. 2024, 25, 2113.

Abstract

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator, triggering various inflammatory conditions, including eosinophil activation and recruitment. Despite the unclear mechanism underlying the formation and maintenance of nasal polyp in chronic rhinosinusitis with nasal polyps (CRSwNP), there is strongly indication of its association with type 2 inflammation. This study aimed to quantify PAF-associated gene expression, examining enzymes involved in PAF synthesis (lysophosphatidylcholine acyltransferase 1 (LPCAT1), LPCAT2, LPCAT3, and LPCAT4), and PAF degradation (PAF acetylhydrolases 1 B2 (PAFAH1B2), PAFAH1B3, and PAF acetylhydrolases 2 (PAFAH2)), and PAF receptor (PTAFR). Transcriptomic analysis encompassed CRSwNP, including eosinophilic CRS (ECRS) (n=9), nonECRS (n=8), and a subgroup of ECRS with aspirin exacerbated respiratory disease (Asp) (n=3) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria. Gene expression profiles from nasal polyps in CRSwNP patients and the uncinate process in normal subjects (controls) (n=6) were analyzed using bulk RNA barcoding and sequencing (BRB-seq). Hierarchal analysis, utilizing the average linkage method with iDEP1.1, clarified the relationship between Differentially Expressed Genes (DEG) expressions and cluster formation. Two clusters (cluster 1 (n=11) and cluster 2 (n=9)) of CRSwNP divided by hierarchal analysis showed distinct gene expression profiles in the specific pathway of “cytokine-cytokine receptor interaction” in KEGG pathway and upregulated type 2 inflammatory gene expression in cluster 2. In CRSwNP subclassification of ECRS, nonECRS, and Ctrl, PTAFR was only upregulated in ECRS and nonECRS. In cluster analysis, cluster 1 showed significant downregulation of LPCAT2 and upregulation of PTAFR expression, while cluster 2 showed significant upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. These findings suggest that cluster 2, characterized by severe type 2 inflammatory gene expression, manifest a prominent PAF-associated pathophysiology. Understanding this high PAF-associated pathophysiology in cluster 2 could provide valuable insights into the treatment and management of CRSwNP.

Keywords

Paranasal sinuses; Chronic rhinosinusitis (CRS); BRB-seq; Nasal polyps; Differentially Expressed Genes (DEG) analysis; Hierarchal analysis; Pathway analysis; Type 2 inflammation; LPCAT1; LPCAT2, PAFAH1B2, PAFAH1B3; PAFAH2; PTAFR

Subject

Medicine and Pharmacology, Otolaryngology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.