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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.00511

Pulmonary Endothelial Mechanical Sensing and Signaling, a Story of Focal Adhesions and Integrins in Ventilator Induced Lung Injury

Gabiel T. Kelly1, Reem Faraj1,  Yao Zhang1,  Ting Wang1*, Emim Maltepe2, Jeffrey Fineman2 and Stephen Black1
  • 1College of Medicine Phoenix, University of Arizona, United States
  • 2University of California, United States

Patients with critical illness such as acute lung injury often undergo mechanical ventilation in the intensive care unit. Though lifesaving in many instances, mechanical ventilation often results in ventilator induced lung injury (VILI), characterized by overdistension of lung tissue leading to release of edemagenic agents, which further damage the lung and contribute to the mortality and progression of pulmonary inflammation. The endothelium is particularly sensitive, as VILI associated mechanical stress results in endothelial cytoskeletal rearrangement, stress fiber formation, and integrity loss. At the heart of these changes are integrin tethered focal adhesions (FAs) which participate in mechanosensing, structure, and signaling. Here we present the known roles of FA proteins including c-Src, talin, FAK, paxillin, vinculin, and integrins in the sensing and response to cyclic stretch and VILI associated stress. Attention is given to how stretch is propagated from the extracellular matrix through integrins to talin and other FA proteins, as well as signaling cascades that include FA proteins, leading to stress fiber formation and other cellular responses. This unifying picture of FAs aids our understanding in an effort to prevent and treat VILI.

Keywords: ARDS (Acute respiratory distress syndrome), VILI (Ventilator Induced Lung Injury), Focal adhesion (FA) complex, Mechanical Stress, Cyclic stretch, Integrin β4

Received: 16 Dec 2018; Accepted: 11 Apr 2019.

Edited by:

Andreea Trache, Texas A&M University, United States

Reviewed by:

Dan Predescu, Rush University, United States
Andrea Moriondo, University of Insubria, Italy  

Copyright: © 2019 Kelly, Faraj, Zhang, Wang, Maltepe, Fineman and Black. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ting Wang, College of Medicine Phoenix, University of Arizona, Phoenix, 85004, Arizona, United States,