PMID- 37740367
OWN - NLM
STAT- MEDLINE
DCOM- 20240108
LR  - 20240108
IS  - 1943-572X (Electronic)
IS  - 0003-4894 (Linking)
VI  - 133
IP  - 2
DP  - 2024 Feb
TI  - Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal 
      Squamous Metaplasia.
PG  - 214-223
LID - 10.1177/00034894231201016 [doi]
AB  - OBJECTIVES: Gain insights into the pathophysiology of idiopathic subglottic 
      stenosis (iSGS) by investigating differences in transcriptome of subglottic 
      mucosal tissue between patients with iSGS and controls, and between tracheal and 
      subglottic tissue within patients. METHODS: RNA sequencing was conducted on 
      biopsied mucosal samples collected from subglottic and tracheal (in-patient 
      control) regions in iSGS patients, and from subglottis in controls. The gene 
      expression differences were validated on a protein level by (1) staining the 
      tissue samples obtained from a second cohort of patients and controls; and (2) in 
      vitro functional assays using primary subglottic epithelial cells from both iSGS 
      patients and healthy donors. RESULTS: We found 7 upregulated genes in the 
      subglottic region of iSGS patients relative to both the tracheal mucosa and 
      subglottic region of controls. A gene ontology enrichment analysis found that the 
      epithelial cell differentiation and cornification pathways are significant, 
      involving specifically 3 of the genes: involucrin (IVL), small proline rich 
      protein 1B (SPRR1B), and keratin 16 (KRT16). Involvement of these pathways 
      suggests squamous metaplasia of the epithelium. Histological analyses of 
      epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of 
      the samples from iSGS patients and in 25% from controls. Immunohistochemical 
      evaluation of the samples presented with squamous epithelium revealed increased 
      expression of the protein encoded by SPRR1B, hyperproliferative basal cells, 
      shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. 
      Cultured primary subglottic epithelial cells from iSGS patients had higher 
      proliferation rates compared to healthy donors and squamous metaplastic 
      differentiation formed thinner epithelia with increased expression proteins 
      encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal 
      cells in iSGS. CONCLUSIONS: Abnormal squamous differentiation of epithelial cells 
      may contribute to the pathogenesis of iSGS. Patients having metaplastic 
      epithelial phenotype may be sensitive to drugs that reverse it to a normal 
      phenotype.
FAU - Tchoukalova, Yourka D
AU  - Tchoukalova YD
AUID- ORCID: 0000-0002-2495-0890
AD  - Head and Neck Regenerative Medicine Laboratory, Mayo Clinic Arizona, Scottsdale, 
      AZ, USA.
FAU - Phung, Tanya N
AU  - Phung TN
AD  - Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA.
AD  - School of Life Sciences, Arizona State University, Tempe, AZ, USA.
AD  - Faculty of Science, Complex Trait Genetics, Vrije Universiteit Amsterdam, 
      Amsterdam, The Netherlands.
FAU - Kennedy, Maeve M
AU  - Kennedy MM
AUID- ORCID: 0000-0001-8343-7707
AD  - Head and Neck Regenerative Medicine Laboratory, Mayo Clinic Arizona, Scottsdale, 
      AZ, USA.
AD  - Baylor College of Medicine, Houston, TX, USA.
FAU - Miranda-Grandjean, Danielle
AU  - Miranda-Grandjean D
AD  - Head and Neck Regenerative Medicine Laboratory, Mayo Clinic Arizona, Scottsdale, 
      AZ, USA.
FAU - Becquer, Emanuel
AU  - Becquer E
AD  - College of Health Solutions, Arizona State University, Phoenix, AZ, USA.
AD  - Contexture, Phoenix, AZ, USA.
FAU - Chen, Longwen
AU  - Chen L
AD  - Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
FAU - Zhang, Nan
AU  - Zhang N
AD  - Department of Quantitative Health Sciences, Mayo, AZ Clinic, Scottsdale, AZ, USA.
FAU - Dinu, Valentin
AU  - Dinu V
AD  - College of Health Solutions, Arizona State University, Phoenix, AZ, USA.
AD  - Department of Basic Medical Sciences, Arizona State University, Phoenix, AZ, USA.
FAU - Wilson, Melissa A
AU  - Wilson MA
AD  - Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA.
AD  - School of Life Sciences, Arizona State University, Tempe, AZ, USA.
AD  - Biodesign Institute, Arizona State University, Tempe, AZ, USA.
FAU - Lott, David G
AU  - Lott DG
AUID- ORCID: 0000-0001-6541-9687
AD  - Head and Neck Regenerative Medicine Laboratory, Mayo Clinic Arizona, Scottsdale, 
      AZ, USA.
AD  - Department of Otolaryngology-Head and Neck Surgery, Division of Laryngology, Mayo 
      Clinic Arizona, Phoenix, AZ, USA.
LA  - eng
PT  - Journal Article
DEP - 20230922
PL  - United States
TA  - Ann Otol Rhinol Laryngol
JT  - The Annals of otology, rhinology, and laryngology
JID - 0407300
RN  - 0 (Cornified Envelope Proline-Rich Proteins)
SB  - IM
MH  - Humans
MH  - Constriction, Pathologic
MH  - *Laryngostenosis/etiology
MH  - *Larynx/pathology
MH  - Cornified Envelope Proline-Rich Proteins
MH  - Metaplasia/complications
MH  - *Carcinoma, Squamous Cell/complications
OTO - NOTNLM
OT  - RNA-seq
OT  - cornified cell envelope
OT  - epithelial cells
OT  - idiopathic subglottic stenosis
OT  - squamous metaplasia
COIS- Declaration of Conflicting InterestsThe author(s) declared no potential conflicts 
      of interest with respect to the research, authorship, and/or publication of this 
      article.
EDAT- 2023/09/23 11:44
MHDA- 2024/01/08 06:42
CRDT- 2023/09/23 00:26
PHST- 2024/01/08 06:42 [medline]
PHST- 2023/09/23 11:44 [pubmed]
PHST- 2023/09/23 00:26 [entrez]
AID - 10.1177/00034894231201016 [doi]
PST - ppublish
SO  - Ann Otol Rhinol Laryngol. 2024 Feb;133(2):214-223. doi: 
      10.1177/00034894231201016. Epub 2023 Sep 22.