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WNT/β-catenin signaling is modulated by mechanical ventilation in an experimental model of acute lung injury.
Intensive Care Med. 2011 Jul; 37(7):1201-9.IC

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+Show Affiliations

CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain, jesus. villar54@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21567117

Citation

Villar, Jesús, et al. "WNT/β-catenin Signaling Is Modulated By Mechanical Ventilation in an Experimental Model of Acute Lung Injury." Intensive Care Medicine, vol. 37, no. 7, 2011, pp. 1201-9.
Villar J, Cabrera NE, Casula M, et al. WNT/β-catenin signaling is modulated by mechanical ventilation in an experimental model of acute lung injury. Intensive Care Med. 2011;37(7):1201-9.
Villar, J., Cabrera, N. E., Casula, M., Valladares, F., Flores, C., López-Aguilar, J., Blanch, L., Zhang, H., Kacmarek, R. M., & Slutsky, A. S. (2011). WNT/β-catenin signaling is modulated by mechanical ventilation in an experimental model of acute lung injury. Intensive Care Medicine, 37(7), 1201-9. https://doi.org/10.1007/s00134-011-2234-0
Villar J, et al. WNT/β-catenin Signaling Is Modulated By Mechanical Ventilation in an Experimental Model of Acute Lung Injury. Intensive Care Med. 2011;37(7):1201-9. PubMed PMID: 21567117.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - WNT/β-catenin signaling is modulated by mechanical ventilation in an experimental model of acute lung injury. AU - Villar,Jesús, AU - Cabrera,Nuria E, AU - Casula,Milena, AU - Valladares,Francisco, AU - Flores,Carlos, AU - López-Aguilar,Josefina, AU - Blanch,Lluis, AU - Zhang,Haibo, AU - Kacmarek,Robert M, AU - Slutsky,Arthur S, Y1 - 2011/05/13/ PY - 2010/07/27/received PY - 2011/03/11/accepted PY - 2011/5/14/entrez PY - 2011/5/14/pubmed PY - 2012/7/21/medline SP - 1201 EP - 9 JF - Intensive care medicine JO - Intensive Care Med VL - 37 IS - 7 N2 - 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. SN - 1432-1238 UR - https://www.unboundmedicine.com/medline/citation/21567117/abstract/WNT/��_catenin_signaling_is_modulated_by_mechanical_ventilation_in_an_experimental_model_of_acute_lung_injury_ L2 - https://dx.doi.org/10.1007/s00134-011-2234-0 DB - PRIME DP - Unbound Medicine ER -