Classic Signaling Pathways in Alveolar Injury and Repair Involved in Sepsis-Induced ALI/ARDS: New Research Progress and Prospect

Abstract

Sepsis is a common critical clinical disease with high mortality that can cause approximately 10 million deaths worldwide each year. Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a common clinical complication of sepsis, which occurs primarily as diffuse alveolar injury, hypoxemia, and respiratory distress. The mortality rate of ALI/ARDS is as high as 30%-40%, which greatly endangers human health. Due to the unclear pathogenesis of ALI/ARDS, its treatment is still a worldwide problem. At present, clinical treatment mainly relies on lung-protective ventilation, prone position ventilation, and fluid management. However, there is a lack of effective and specific treatment measures. In recent years, domestic and foreign scholars have committed to basic research on ALI/ARDS, trying to further clarify its pathogenesis and find new targets and methods for the treatment of ALI/ARDS. In this review, we summarize the signaling pathways related to alveolar injury and repair in sepsis-induced ALI/ARDS and their latest research progress. They include the NF-κB, JAK2/STAT3, mitogen-activated protein kinase (MAPK), mTOR, and Notch signaling pathways. Understanding the molecular mechanisms of these signaling pathways in sepsis-induced ALI/ARDS may provide new targets and ideas for the clinical treatment of this disease.

Bioinformatics and system biology approach to identify the influences among COVID-19, ARDS and sepsis

“…Acute respiratory distress syndrome (ARDS) is a serious respiratory disease secondary to trauma, shock, infection and other non-cardiogenic diseases. ARDS is one of the most common and serious complications in the development of sepsis ( 11 ). The mortality rate of ARDS is as high as 30%-40% ( 11 ).…”

Recombinant GM-CSF for diseases of GM-CSF insufficiency: Correcting dysfunctional mononuclear phagocyte disorders

“…Release of antiviral pro-inflammatory immune response molecules into the systemic circulation can result in sepsis and can lead to ARDS ( 166 ). In animal models of post-viral ARDS, murine GM-CSF demonstrated immunomodulatory effects that improved the clinical response and symptoms associated with viral respiratory infections ( 167 , 168 ).…”

Echinacea Polyphenols Inhibit NLRP3-Dependent Pyroptosis, Apoptosis, and Necroptosis via Suppressing NO Production during Lipopolysaccharide-Induced Acute Lung Injury

“…Previous studies have shown that PANoptosis was closely related to lung injury. 3,15 During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, patients develop systemic symptoms of varying severity and induce PANoptosis, leading to further exacerbation of the pulmonary cytokine storm, and COVID-19associated pneumonia can progress to ARDS. 5,16,17 Because of the complexity of PANoptosis, the treatment maybe fails if three PCDs in PANoptosis cannot be simultaneously inhibited to prevent the compensatory activation of other pathways.…”

“…Acute lung injury (ALI) is one of the most common and intractable critical diseases with high mortality, and it has recently been rediagnosed as mild or moderate acute respiratory distress syndrome (ARDS). , A major cause of ALI/ARDS is sepsis, and there are nearly 50 million cases of sepsis and 11 million sepsis-related deaths worldwide per year. , A recent global survey reported that the mortality from coronavirus disease 2019 (COVID-19) has soared to 45% because more than 30% of patients has complications from ARDS . Currently, the treatment of ALI/ARDS is mainly supportive such as oxygen therapy, noninvasive mechanical ventilation, and other respiratory support treatments, and there is no specific treatment .…”

“…PANoptosis is a complex form of inflammatory programmed cell death (PCD) pathway that involves pyroptosis, apoptosis, and necroptosis, whereas it cannot be characterized by any of these three PCD pathways alone. , PANoptosis has been elucidated in a variety of conditions ranging from normal development to microbial infectious, autoimmune diseases, cytokine storm, and cancer. Previous studies have shown that PANoptosis was closely related to lung injury. , During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, patients develop systemic symptoms of varying severity and induce PANoptosis, leading to further exacerbation of the pulmonary cytokine storm, and COVID-19-associated pneumonia can progress to ARDS. ,, Because of the complexity of PANoptosis, the treatment maybe fails if three PCDs in PANoptosis cannot be simultaneously inhibited to prevent the compensatory activation of other pathways. However, no research focused on a certain drug or treatment to simultaneously inhibit the three arms of PANoptosis process in ALI.…”