Tenascin-C inactivation impacts lung structure and function beyond lung development.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_DEC139B09B27
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Tenascin-C inactivation impacts lung structure and function beyond lung development.
Périodique
Scientific reports
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
20/03/2020
Peer-reviewed
Oui
Volume
10
Numéro
1
Pages
5118
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
Tenascin-C (TNC) is an extracellular matrix protein expressed at high levels during lung organogenesis. Later, TNC is only transiently de novo expressed to orchestrate tissue repair in pathological situations. We previously showed that TNC inactivation affects lung development and thus evaluated here the implications on lung function in newborn/adult mice. Respiratory function parameters were measured in anesthetized and mechanically ventilated wild-type (WT) and TNC-deficient mice at 5 (P5) and 90 (P90) days of age under basal conditions, as well as following high tidal volume (HTV) ventilation. At P5, TNC-deficient mice showed an increased static compliance (Cst) and inspiratory capacity (IC) relative to WT at baseline and throughout HTV. At P90, however, Cst and IC were only elevated at baseline. Control non-ventilated newborn and adult TNC-deficient mice showed similar lung morphology, but less alpha smooth muscle actin (α-SMA) around small airways. SMA + cells were decreased by 50% in adult TNC-deficient lungs and collagen layer thickened around small airways. Increased surfactant protein C (SP-C) and altered TGFβ and TLR4 signaling pathways were also detected. Thus, TNC inactivation-related defects during organogenesis led to persisting functional impairment in adulthood. This might be of interest in the context of pulmonary diseases with thickened airway smooth muscle layer or ventilation heterogeneity, like asthma and COPD.
Mots-clé
Actins/metabolism, Animals, Cell Proliferation, Collagen/metabolism, Extracellular Matrix/metabolism, Lung/anatomy & histology, Lung/growth & development, Lung/pathology, Mice, Mice, Knockout, Organogenesis/genetics, Organogenesis/physiology, Pulmonary Surfactant-Associated Protein C/metabolism, Respiration, Artificial, Signal Transduction/physiology, Tenascin/genetics, Tenascin/metabolism, Tidal Volume/genetics, Tidal Volume/physiology, Toll-Like Receptor 4/metabolism, Transforming Growth Factor beta/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/04/2020 20:54
Dernière modification de la notice
08/08/2024 7:41