Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis.

Autor:	Direder M; Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.; Aposcience AG, Vienna, Austria.; Department of Orthopedics and Trauma-Surgery, Medical University of Vienna, Vienna, Austria., Laggner M; Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.; Aposcience AG, Vienna, Austria., Copic D; Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.; Aposcience AG, Vienna, Austria.; Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria., Klas K; Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.; Aposcience AG, Vienna, Austria., Bormann D; Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.; Aposcience AG, Vienna, Austria., Schweiger T; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria., Hoetzenecker K; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria., Aigner C; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria., Ankersmit HJ; Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology, Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.; Aposcience AG, Vienna, Austria.; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria., Mildner M; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2024 Jul 12; Vol. 12, pp. 1380902. Date of Electronic Publication: 2024 Jul 12 (Print Publication: 2024).
DOI:	10.3389/fcell.2024.1380902
Abstrakt:	Idiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS. Competing Interests: Authors MD, ML, DC, KK, DB, and HA were employed by Aposcience AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Direder, Laggner, Copic, Klas, Bormann, Schweiger, Hoetzenecker, Aigner, Ankersmit and Mildner.)
Databáze:	MEDLINE
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