PMID- 37622571
OWN - NLM
STAT- MEDLINE
DCOM- 20231225
LR  - 20240229
IS  - 1097-6817 (Electronic)
IS  - 0194-5998 (Print)
IS  - 0194-5998 (Linking)
VI  - 170
IP  - 1
DP  - 2024 Jan
TI  - Murine Model of Airway Fibrosis has Anatomic, Physiologic, and Molecular 
      Congruency to Human iSGS.
PG  - 179-186
LID - 10.1002/ohn.502 [doi]
AB  - OBJECTIVE: To narrow knowledge gaps in the pathophysiology of idiopathic 
      subglottic stenosis (iSGS) through comparison of a murine subglottic stenosis 
      model with iSGS. STUDY DESIGN: In vivo animal study. SETTING: Academic 
      institution. METHODS: Murine samples/measurements were obtained from mice that 
      underwent chemomechanical injury with a wire brush and bleomycin. Human 
      samples/measurements were obtained from iSGS patients. Anatomic, physiologic, and 
      epithelial molecular data were collected using histology, human peak expiratory 
      flow (PEF) and murine airway conductance, gene expression analysis with 
      quantitative polymerase chain reaction, and protein analysis with quantitative 
      immunohistochemistry. RESULTS: Anatomic patterns of scars at the subglottis and 
      proximal trachea seen in the murine model are similar to iSGS patients. 
      Subglottic stenosis (SGS) mice had a decrease (P = .0194) in airway conductance 
      compared to healthy controls, similar to a decrease (P = .0001) in predilation 
      PEF versus postdilation in iSGS patients. There was decreased epithelial gene 
      expression of E-cadherin (ECAD) (P < 0.01), occludin (OCLN) (P < .01), and 
      cytokeratin-5 (CK5) (P < .05) and protein expression of ECAD (H/M: P < .001), 
      OCLN (H: P < 0.05, M: P < .001), and CK5 (H: P < .001, M: P < .01) in murine SGS 
      and iSGS versus controls. CONCLUSION: The murine SGS model shows anatomic, 
      physiologic, and molecular congruency with human iSGS, making it a reasonable 
      model to investigate iSGS. The molecular similarities in epithelial barrier 
      dysfunction suggest it may best be suited to explore epithelial mechanisms of 
      iSGS and therapies directed at epithelial reconstitution. This model provides a 
      foundation to collect data that will improve understanding of iSGS, and, 
      ultimately, translate into more accurate animal models for future use.
CI  - (c) 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.
FAU - Mafla, Laura M
AU  - Mafla LM
AUID- ORCID: 0000-0002-9319-5761
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
FAU - Ospino, Rafael
AU  - Ospino R
AUID- ORCID: 0000-0002-8501-1934
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
FAU - So, Raymond J
AU  - So RJ
AUID- ORCID: 0000-0003-1004-7606
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
FAU - Berges, Alexandra J
AU  - Berges AJ
AUID- ORCID: 0000-0002-0890-6291
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
FAU - Collins, Samuel L
AU  - Collins SL
AUID- ORCID: 0000-0002-0292-6937
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
FAU - Chan-Li, Yee
AU  - Chan-Li Y
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
FAU - Abd-Elazem, Ibrahim
AU  - Abd-Elazem I
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
FAU - Motz, Kevin
AU  - Motz K
AUID- ORCID: 0000-0002-9255-7265
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
FAU - Hillel, Alexander T
AU  - Hillel AT
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, USA.
LA  - eng
GR  - R01 DC018567/DC/NIDCD NIH HHS/United States
GR  - R56 DC020736/DC/NIDCD NIH HHS/United States
PT  - Journal Article
DEP - 20230825
PL  - England
TA  - Otolaryngol Head Neck Surg
JT  - Otolaryngology--head and neck surgery : official journal of American Academy of 
      Otolaryngology-Head and Neck Surgery
JID - 8508176
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Constriction, Pathologic
MH  - Disease Models, Animal
MH  - *Pulmonary Fibrosis/pathology
MH  - *Laryngostenosis/surgery
MH  - *Larynx/pathology
MH  - Fibrosis
PMC - PMC10897762
MID - NIHMS1969596
OTO - NOTNLM
OT  - cricotracheal
OT  - iSGS
OT  - idiopathic
OT  - murine model
OT  - stenosis
COIS- Competing interests: None.
EDAT- 2023/08/25 12:42
MHDA- 2023/12/25 06:42
PMCR- 2025/01/01
CRDT- 2023/08/25 07:22
PHST- 2023/07/03 00:00 [revised]
PHST- 2023/03/10 00:00 [received]
PHST- 2023/07/24 00:00 [accepted]
PHST- 2025/01/01 00:00 [pmc-release]
PHST- 2023/12/25 06:42 [medline]
PHST- 2023/08/25 12:42 [pubmed]
PHST- 2023/08/25 07:22 [entrez]
AID - 10.1002/ohn.502 [doi]
PST - ppublish
SO  - Otolaryngol Head Neck Surg. 2024 Jan;170(1):179-186. doi: 10.1002/ohn.502. Epub 
      2023 Aug 25.