PMID- 35948078
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231028
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 192
IP  - 11
DP  - 2022 Nov
TI  - RNA Sequencing of Idiopathic Subglottic Stenosis Tissues Uncovers Putative 
      Profibrotic Mechanisms and Identifies a Prognostic Biomarker.
PG  - 1506-1530
LID - S0002-9440(22)00213-9 [pii]
LID - 10.1016/j.ajpath.2022.07.005 [doi]
AB  - Idiopathic subglottic stenosis (iSGS) is a localized airway disease that almost 
      exclusively affects females. Understanding the molecular mechanisms involved may 
      provide insights leading to therapeutic interventions. Next-generation sequencing 
      was performed on tissue sections from patients with iSGS (n = 22), antineutrophil 
      cytoplasmic antibody-associated vasculitis (AAV; n = 5), and matched controls (n 
      = 9) to explore candidate genes and mechanisms of disease. Gene expression 
      changes were validated, and selected markers were identified by 
      immunofluorescence staining. Epithelial-mesenchymal transition (EMT) and 
      leukocyte extravasation pathways were the biological mechanisms most relevant to 
      iSGS pathogenesis. Alternatively activated macrophages (M2) were abundant in the 
      subepithelium and perisubmucosal glands of the airway in iSGS and AAV. Increased 
      expression of the mesenchymal marker S100A4 and decreased expression of the 
      epithelial marker epithelial cell adhesion molecule (EPCAM) further supported a 
      role for EMT, but to different extents, in iSGS and antineutrophil cytoplasmic 
      antibody-associated subglottic stenosis. In patients with iSGS, high expression 
      of prostate transmembrane protein, androgen induced 1 (PMEPA1), an EMT regulator, 
      was associated with a shorter recurrence interval (25 versus 116 months: hazard 
      ratio = 4.16; P = 0.041; 95% CI, 1.056-15.60). Thus, EMT is a key pathogenetic 
      mechanism of subglottic stenosis in iSGS and AAV. M2 macrophages contribute to 
      the pathogenesis of both diseases, suggesting a shared profibrotic mechanism, and 
      PMEPA1 may be a biomarker for predicting disease recurrence in iSGS.
CI  - Copyright (c) 2022 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Zhang, Chujie
AU  - Zhang C
AD  - Division of Pulmonary and Critical Care Medicine and Thoracic Diseases Research 
      Unit, Mayo Clinic, Rochester, Minnesota; Department of Respiratory and Critical 
      Care Medicine, West China School of Medicine and West China Hospital, Sichuan 
      University, Chengdu, China.
FAU - Wang, Shaohua
AU  - Wang S
AD  - Division of Pulmonary and Critical Care Medicine and Thoracic Diseases Research 
      Unit, Mayo Clinic, Rochester, Minnesota.
FAU - Casal Moura, Marta
AU  - Casal Moura M
AD  - Division of Pulmonary and Critical Care Medicine and Thoracic Diseases Research 
      Unit, Mayo Clinic, Rochester, Minnesota.
FAU - Yi, Eunhee S
AU  - Yi ES
AD  - Departments of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, 
      Minnesota.
FAU - Bowen, Andrew J
AU  - Bowen AJ
AD  - Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota.
FAU - Specks, Ulrich
AU  - Specks U
AD  - Division of Pulmonary and Critical Care Medicine and Thoracic Diseases Research 
      Unit, Mayo Clinic, Rochester, Minnesota.
FAU - Warrington, Kenneth J
AU  - Warrington KJ
AD  - Division of Rheumatology, Mayo Clinic, Rochester, Minnesota.
FAU - Bayan, Semirra L
AU  - Bayan SL
AD  - Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota.
FAU - Ekbom, Dale C
AU  - Ekbom DC
AD  - Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota.
FAU - Luo, Fengming
AU  - Luo F
AD  - Department of Respiratory and Critical Care Medicine, West China School of 
      Medicine and West China Hospital, Sichuan University, Chengdu, China.
FAU - Edell, Eric S
AU  - Edell ES
AD  - Division of Pulmonary and Critical Care Medicine and Thoracic Diseases Research 
      Unit, Mayo Clinic, Rochester, Minnesota.
FAU - Kasperbauer, Jan L
AU  - Kasperbauer JL
AD  - Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota.
FAU - Vassallo, Robert
AU  - Vassallo R
AD  - Division of Pulmonary and Critical Care Medicine and Thoracic Diseases Research 
      Unit, Mayo Clinic, Rochester, Minnesota. Electronic address: 
      vassallo.robert@mayo.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220807
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (PMEPA1 protein, human)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Male
MH  - Female
MH  - Humans
MH  - Constriction, Pathologic
MH  - *Antibodies, Antineutrophil Cytoplasmic
MH  - Prognosis
MH  - *Laryngostenosis/genetics/pathology
MH  - Sequence Analysis, RNA
MH  - Membrane Proteins/genetics
EDAT- 2022/08/11 06:00
MHDA- 2023/10/23 00:43
CRDT- 2022/08/10 19:23
PHST- 2022/03/10 00:00 [received]
PHST- 2022/06/30 00:00 [revised]
PHST- 2022/07/14 00:00 [accepted]
PHST- 2023/10/23 00:43 [medline]
PHST- 2022/08/11 06:00 [pubmed]
PHST- 2022/08/10 19:23 [entrez]
AID - S0002-9440(22)00213-9 [pii]
AID - 10.1016/j.ajpath.2022.07.005 [doi]
PST - ppublish
SO  - Am J Pathol. 2022 Nov;192(11):1506-1530. doi: 10.1016/j.ajpath.2022.07.005. Epub 
      2022 Aug 7.