The protective effect of PPARγ in sepsis-induced acute lung injury via inhibiting PTEN/β-catenin pathway (Publication with Expression of Concern. See vol. 40, 2020)

The present study aims to reveal the molecular mechanism of peroxisome proliferator-activated receptor gamma (PPAR gamma) on sepsis-induced acute lung injury (ALI). To do that, the rat injury model was established using cecal ligation and perforation (CLP) method, followed by different treatments, and the rats were divided into Sham group, CLP group, CLP + rosiglitazone (PPAR gamma agonist) group, CLP + GW9662 (PPAR gamma inhibitor) group, CLP + bpV (phosphatase and tensin homolog (PTEN) inhibitor) group, CLP + GW9662 + bpV group. Compared with Sham group, the mRNA and protein expression levels of PPAR gamma were down-regulated, the inflammation levels were elevated, and the apoptosis was increased in CLP group. After treatment with rosiglitazone, the protein expression level of PPAR gamma was significantly up-regulated, the phosphorylation level of PTEN/beta-catenin pathway was decreased, the PTEN/beta-catenin pathway was inhibited, the lung injury, inflammation and apoptosis were reduced. The opposite effect was observed after treatment with GW9662. Besides, bpV inhibited PTEN/beta-catenin pathway, and relieved the lung tissue injury. The overexpression of PPAR gamma reduced inflammatory response and inhibited apoptosis in sepsis-induced ALI. Furthermore, PPAR gamma relieved the sepsis-induced ALI by inhibiting the PTEN/beta-catenin pathway.