WNT/β-catenin signaling is modulated by mechanical ventilation in an experimental model of acute lung injury.

Abstract

PURPOSE:

The mechanisms involved in lung injury progression during acute lung injury (ALI) are still poorly understood. Because WNT/β-catenin signaling has been shown to be involved in epithelial cell injury and hyperplasia during inflammation and sepsis, we hypothesized that it would be modulated by mechanical ventilation (MV) in an experimental model of sepsis-induced ALI.

METHODS:

This study was a prospective, randomized, controlled animal study performed using adult male Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation. At 18 h, surviving animals were randomized to spontaneous breathing or two strategies of MV for 4 h: low tidal volume (V (T)) (6 ml/kg) plus 10 cmH2O of positive end-expiratory pressure (PEEP) versus high (20 ml/kg) tidal volume (V (T)) with zero PEEP. Histological evaluation, measurements of WNT5A, total β-catenin, and matrix metalloproteinase-7 (MMP7) protein levels by Western blot, and their immunohistochemical localization in the lungs were analyzed.

RESULTS:

Sepsis and high-V (T) MV caused lung inflammation and perivascular edema with cellular infiltrates and collagen deposition. Protein levels of WNT5A, β-catenin, and MMP7 in the lungs were increased in animals with sepsis-induced ALI. High-V (T) MV was associated with higher levels of WNT5A, β-catenin, and MMP7 protein levels (p < 0.001), compared to healthy control animals. By contrast, low-V (T) MV markedly reduced WNT5A, β-catenin, and MMP7 protein levels (p < 0.001).

CONCLUSIONS:

Our findings demonstrate that the WNT/β-catenin signaling pathway is modulated early during sepsis and ventilator-induced lung injury, suggesting that activation of this pathway could play an important role in both lung injury progression and repair.

• Authors: Jesús Villar, Nuria E Cabrera, Milena Casula, Francisco Valladares, Carlos Flores, Josefina López-Aguilar, Lluis Blanch, Haibo Zhang, Robert M Kacmarek, Arthur S Slutsky
• Journal: Intensive care medicine (Intensive Care Med) Vol. 37 Issue 7 Pg. 1201-9 (Jul 2011) ISSN: 1432-1238 [Electronic] United States
• PMID: 21567117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Wnt Proteins
• beta Catenin
• Matrix Metalloproteinase 7

Topics

• Animals
• Blotting, Western
• Disease Progression
• Immunohistochemistry
• Male
• Matrix Metalloproteinase 7 (metabolism)
• Prospective Studies
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Sepsis (metabolism, physiopathology)
• Signal Transduction
• Ventilator-Induced Lung Injury (metabolism, physiopathology)
• Ventilators, Mechanical
• Wnt Proteins (metabolism)
• beta Catenin (metabolism)