Plasma membrane wounding and repair in pulmonary diseases

Abstract

Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inflammation, pathogen products, environmental exposures, and gastric acid aspiration stress lung cells, and the compromise of plasma membranes occurs as a result. The mechanisms necessary for cells to repair plasma membrane defects have been extensively investigated in the last two decades, and some of these key repair mechanisms are also shown to occur following lung cell injury. Because it was theorized that lung wounding and repair are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF), in this review, we summarized the experimental evidence of lung cell injury in these two devastating syndromes and discuss relevant genetic, physical, and biological injury mechanisms, as well as mechanisms used by lung cells for cell survival and membrane repair. Finally, we discuss relevant signaling pathways that may be activated by chronic or repeated lung cell injury as an extension of our cell injury and repair focus in this review. We hope that a holistic view of injurious stimuli relevant for ARDS and IPF could lead to updated experimental models. In addition, parallel discussion of membrane repair mechanisms in lung cells and injury-activated signaling pathways would encourage research to bridge gaps in current knowledge. Indeed, deep understanding of lung cell wounding and repair, and discovery of relevant repair moieties for lung cells, should inspire the development of new therapies that are likely preventive and broadly effective for targeting injurious pulmonary diseases.

Surfactant replacement therapy reduces acute lung injury and collapse induration-related lung remodeling in the bleomycin model

“…In this regard it has been demonstrated in animal models that an isolated injury of AE2 cells or disruption of the surfactant system is either sufficient to induce a fibrotic lung remodeling (40,51,62,71,72) or results in a higher susceptibility for injury and fibrotic remodeling (69). Although the role of mechanical stress resulting from alveolar R/D and volutrauma is appreciated as an aggravating factor of lung injury in the context of ventilator-induced lung injury (11,50,63), the relevance for disease progression from acute lung injury to tissue remodeling and fibrosis during spontaneous breathing is less clear and therefore represents a gap of knowledge in the context of human diseases characterized by high surface tension, ongoing lung injury, and remodeling (20). In the present study we tested the hypothesis whether surfactant dysfunction is involved in aggravating/ triggering lung injury and remodeling processes such as collapse induration during the time course of disease progression.…”

“…Hence, SRT modifies disease progression to collapse induration. surfactant; collapse induration; lung injury and fibrosis; stereology; bleomycin MECHANICAL STRESS is well accepted to contribute to the pathogenesis of acute lung injury in particular in the context of ventilator-induced lung injury where mechanical ventilation can aggravate preexisting early stages of lung injury (11,50). Harmful stresses operating on lung parenchyma result from atelectrauma and volutrauma (63).…”

High-dose dexamethasone induced LPS-stimulated rat alveolar macrophages apoptosis

“… 28 TGF-β signaling plays vital roles in mediating pulmonary fibrosis when excessive repair appears. 29 Wang et al reported that multiwall carbon nanotubes could promote pulmonary fibrosis through TGF-β/Smad signaling pathway. 30 Our data showed that after being stimulated by a relatively higher dose of Dex (10 −4 M) for 48 hours, TGF-β was significantly higher compared with that in other groups.…”

Cellular mechanisms and signals that coordinate plasma membrane repair

“…While there are in-depth reviews of tissue level repair pathways [154,155], single cell plasma membrane repair has often been viewed as an event unrelated to tissue repair. In recent years the importance of plasma membrane repair in the pathophysiology of disease in many tissues has been appreciated [4,156]. It is also clear that overlapping mechanisms exist between the repair processes at the single cell and tissue scale [157].…”