Clusterin ameliorates LPS-induced ARDS by inhibiting the Wnt/β-catenin pathway.

Acute respiratory distress syndrome (ARDS) is a critical illness characterized by endothelial barrier damage, and the present study investigates the specific role of clusterin (CLU). The study found that CLU concentrations were significantly lower in ARDS patients, particularly non-survivors, compared with non-ARDS patients and survivors; similarly, serum CLU levels were decreased in mice with lipopolysaccharide-induced ARDS. Both in vivo and in vitro experiments demonstrated that treatment with recombinant CLU protein significantly alleviated organ injury and suppressed the inflammatory response. Mechanistically, CLU improves mitochondrial oxidative phosphorylation by inhibiting the Wnt/β-catenin signaling pathway, thereby inhibiting the expression of inflammatory factors, repairing adherens junctions, and reducing vascular leakage, ultimately preserved intercellular junction protein expression. In summary, CLU ameliorates endothelial injury in ARDS models by inhibiting the Wnt/β-catenin pathway, playing a crucial protective role in host defense against ARDS.