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

Conclusion Ventilator induced lung injury is characterized by compromised vascular endothelial barrier protection and the production of edemagenic agents in response to mechanical stretch that may lead to overdistention depending upon tidal volume and ventilation frequency (Dos Santos and S.sky, 2000; Lionetti et al., 2005; Birukova et al., 2006). This mechanical-force initiated cellular injury results in cytoskeletal rearrangement. FAs play a central role in mechanotransduction and cytoskeletal rearrangement (De et al., 2010; Ladoux and Nicolas, 2012; Iskratsch et al., 2014; De, 2018). Here, we present the known picture of the molecular changes that occur at FAs as a result of CS and other factors of VILI. Within the FA, force from stretching of the ECM is propagated through integrins into the FA (Geiger et al., 2009). This force is then exerted on adapter and signaling proteins such as talin and vinculin. Additionally, other receptors for stretch and agents involved in VILI result in phosphorylation events on c-Src and then on integrin, FAK, paxillin, and others. Together these lead to the characteristic stress fiber formation and cytoskeletal rearrangement seen in VILI. The most essential proteins within the FA are integrins and talin (Jiang et al., 2003). These are the minimum structural components which link the ECM to the actin cytoskeleton. Talin may be considered the master regulator of FAs (Klapholz and Brown, 2017), but integrins anchor the FA to the plasma membra...
Source: Frontiers in Physiology - Category: Physiology Source Type: research