Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research

Abstract

Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.

The sirtuin family in health and disease

“…Lung injury: Acute lung injury (ALI) is a potentially life threatening and devastating disease with an extremely high rate of mortality. 636 It is a clinical syndrome associated with respiratory dysfunction and is often a complication of sepsis. 637 Additionally, ALI can develop into acute respiratory distress syndrome in more serious injuries, which lacks novel and efficient therapies.…”

B2M is a Biomarker Associated With Immune Infiltration In High Altitude Pulmonary Edema

“…After collecting the lung tissues, the wet weight of the lungs was measured (Quintix223-1CN, division value, d = 1mg; Sartorius, Sartorius Scientific Instruments Co., Ltd., Beijing, China). The tissues were then placed in an oven at a constant temperature of 50° C for 72 hours to obtain their constant weight by Elliot formula [ 31 ], LWC percentage water content (%) = [(wet weight - dry weight)/ wet weight] × 100% [ 32 ];Modeling weight change = weight after modeling (g) - weight before modeling (g); Lung coefficient = wet weight of both lungs (g)/ body weight (kg) [ 33 ].…”

Alveolar-capillary endocytosis and trafficking in acute lung injury and acute respiratory distress syndrome

“…It is noteworthy that LPS modulates the Cav-1/nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cell (NF-κB) axis in vivo . Downregulation of Cav-1 in mice in LPS-induced ALI reduced inflammation by decreasing expression levels of CD3 and the adhesion family member F4/80, activated autophagy by inhibiting AKT/mTOR, and promoted AMP-activated protein kinase signaling, thereby improving lung morphology and function ( 79 ).…”