Abstract
The present study aims to reveal the molecular mechanism of peroxisome proliferator-activated receptor γ (PPARγ) 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 (PPARγ agonist) group, CLP + GW9662 (PPARγ 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 PPARγ 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 PPARγ was significantly up-regulated, the phosphorylation level of PTEN/β-catenin pathway was decreased, the PTEN/β-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/β-catenin pathway, and relieved the lung tissue injury. The overexpression of PPARγ reduced inflammatory response and inhibited apoptosis in sepsis-induced ALI. Furthermore, PPARγ relieved the sepsis-induced ALI by inhibiting the PTEN/β-catenin pathway.
Highlights
Sepsis is an organic disease induced by abnormal host reaction to infection [1]
Based on the rat model, reduced inflammation is the optimal target of molecular therapy for sepsis-induced acute lung injury (ALI) [22]
Canikli et al showed that the apoptosis was significantly increased in epithelial cell of sepsis-induced ALI [26]
Summary
Sepsis-induced acute lung injury (ALI) is proved to commonly lead a higher mortality rate than other causes of ALI [2,3]. The mRNA expression of PPARγ in lung tissues is decreased in ALI mice, and keeps at a low level at the end of the observation period [7]. The increased expression of PPARγ is critical to protect against ALI in mice [8]. Brenneis et al have indicated that the expression of PPARγ in T cells can be used as a prognostic marker of sepsis [10]. The biological function of PPARγ in disease progression is commonly realized by targeting certain genes or pathways such as phosphatase and tensin homolog (PTEN) and PTEN/β-catenin pathway [13,14].
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