Emerging roles of mechanosensitive ion channels in acute lung injury/acute respiratory distress syndrome

Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a devastating respiratory disorder with high rates of mortality and morbidity, but the detailed underlying mechanisms of ALI/ARDS remain largely unknown. Mechanosensitive ion channels (MSCs), including epithelial sodium channel (ENaC), Piezo channels, transient receptor potential channels (TRPs), and two-pore domain potassium ion (K2P) channels, are highly expressed in lung tissues, and the activity of these MSCs can be modulated by mechanical forces (e.g., mechanical ventilation) and other stimuli (e.g., LPS, hyperoxia). Dysfunction of MSCs has been found in various types of ALI/ARDS, and MSCs play a key role in regulating alveolar fluid clearance, alveolar epithelial/endothelial barrier function, the inflammatory response and surfactant secretion in ALI/ARDS lungs. Targeting MSCs exerts therapeutic effects in the treatment of ALI/ARDS. In this review, we summarize the structure and functions of several well-recognized MSCs, the role of MSCs in the pathogenesis of ALI/ARDS and recent advances in the pharmacological and molecular modulation of MSCs in the treatment of ALI/ARDS. According to the current literature, targeting MSCs might be a very promising therapeutic approach against ALI/ARDS.

Fortunellin ameliorates LPS‐induced acute lung injury, inflammation, and collagen deposition by restraining the TLR4/NF‐κB/NLRP3 pathway

“…ALI is the prevalent respiratory disease of acute inflammation with high morbidity and mortality. 1 , 2 An effective strategy for ALI therapy still needs to be developed due to the continuously increasing drug resistance and the emergence of new pathogens. 6 Fortunellin has anti‐inflammation properties, 7 , 9 , 10 while its role in ALI progression remains elusive.…”

“…Acute lung injury (ALI) is a severe respiratory disease with high morbidity and mortality annually 1 . It is featured by excessive inflammation, alveolar‐capillary barrier disruption, gas exchange impairment, and pulmonary edema 2–4 .…”

“…Acute lung injury (ALI) is a severe respiratory disease with high morbidity and mortality annually. 1 It is featured by excessive inflammation, alveolar‐capillary barrier disruption, gas exchange impairment, and pulmonary edema. 2 , 3 , 4 ALI has a complex etiology and can be caused by sepsis, pneumonia, burns, chest trauma, and other factors.…”

Evaluation of interleukin‐1 and interleukin‐6 receptor antagonists in a murine model of acute lung injury

“…Due to the importance of the lesional component of ARDS (Butt et al., 2016; Matthay et al., 2019; Monahan, 2013), the development of novel therapeutic approaches that promote the restoration of alveolar integrity and function, for example, with mesenchymal stromal cells (Wick et al., 2021) or by targeting key proteins involved in epithelial repair processes, is critical for ARDS recovery, before the establishment of irreversible fibrosis. Compelling evidence suggests that a class of membrane proteins, that is, K + channels, play an important role in epithelial repair and play a protective role in animal models of epithelial injury (Abe et al., 2020; Arni et al., 2021; Girault & Brochiero, 2014; He et al., 2019; Jia et al., 2022; Schwingshackl et al., 2017; Trinh et al., 2007, 2008; Zhou et al., 2019; Zyrianova et al., 2020). KvLQT1 and K ATP K + channels also regulate alveolar fluid clearance in vitro and in vivo (Abe et al., 2020; Aubin Vega et al., 2023; Bardou et al., 2012; Leroy et al., 2006; Sakuma et al., 1998; Zhou et al., 2019).…”

Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications

“…Damage to the alveolar epithelial-endothelial barrier, where gas exchange occurs in the lung, leads to the accumulation of proteinaceous fluid filled with proteins and cells in the alveolar space. This disrupts alveolar gas exchange, resulting in severe lung dysfunction [222][223][224]. Pathological specimens from ALI/ARDS patients often reveal diffuse alveolar damage characterized by alterations in endothelial and epithelial cells [225].…”