Tenascin-C inactivation impacts lung structure and function beyond lung development

Area of Science:

• Pulmonary Medicine
• Developmental Biology
• Extracellular Matrix Biology

Background:

• Tenascin-C (TNC) is crucial during lung development and transiently expressed for tissue repair.
• Previous studies indicated TNC inactivation impacts lung development.
• The functional consequences of TNC deficiency on lung mechanics were not fully understood.

Purpose of the Study:

• To investigate the long-term effects of Tenascin-C (TNC) deficiency on respiratory function in mice.
• To assess lung mechanics in TNC-deficient mice from newborn to adult stages.
• To explore the underlying molecular and structural changes associated with TNC inactivation.

Main Methods:

• Respiratory function parameters were measured in wild-type (WT) and TNC-deficient mice at postnatal day 5 (P5) and 90 (P90).
• Measurements were taken under basal conditions and following high tidal volume (HTV) ventilation.
• Lung morphology, alpha smooth muscle actin (α-SMA) expression, collagen deposition, and signaling pathways (TGFβ, TLR4) were analyzed.

Main Results:

• TNC-deficient mice exhibited increased static compliance (Cst) and inspiratory capacity (IC) at P5, persisting under HTV ventilation.
• At P90, elevated Cst and IC were observed only under basal conditions.
• TNC deficiency led to reduced α-SMA around small airways, thickened collagen layers, increased surfactant protein C (SP-C), and altered TGFβ/TLR4 signaling.

Conclusions:

• TNC inactivation during lung organogenesis results in persistent functional deficits into adulthood.
• Altered airway smooth muscle and extracellular matrix composition contribute to impaired lung function.
• These findings are relevant for understanding pulmonary diseases like asthma and COPD characterized by airway remodeling and ventilation heterogeneity.