LPS Promoted HPMEC Autophagy by Suppression of the PI3K/Akt/mTOR through Inhibited TIMAP-Promoted Moesin Expression in Sepsis

Abstract

Background: During sepsis, multiorgan failure often results as the body responds to infection. Lipopolysaccharides (LPS) are major players in the induction of sepsis. Because autophagy can protect against multiple organ dysfunction during sepsis, we explored LPS’s regulatory role in autophagy and its interaction with transforming growth factor (TGF)-β inhibited membrane associated protein (TIMAP), moesin, and the Wnt β-catenin signaling pathway in human pulmonary microvascular endothelial cells (HPMECs). Methods: Bioinformatics was used to screen for autophagy genes. HPMECs were selected for by determination of cell proliferation and LPS-induced autophagy. Enrichment of TIMAP and moesin was detected by chromatin immunoprecipitation (ChIP)-PCR (polymerase chain reaction). Results: LPS promoted autophagy in HPMECs, which resulted in the inhibition of TIMAP’s expression. Moesin expression was then activated by inhibited TIMAP in HPMECs treated with LPS. LPS promoted HPMECs’ autophagy by the suppression of the phosphatidylinositol-3-kinase (PI3K)/Akt (protein kinase B)/mammalian target of rapamycin (mTOR) signaling pathway via inhibited-TIMAP-promoted-moesin expression. Conclusions: The LPS-TIMAP-moesin-PI3K/Akt/mTOR axis is involved in a protective capacity in the autophagy of HPMECs. Specifically, LPS prevented TIMAP’s expression, upregulated moesin’s expression, and inhibited the PI3K/Akt/mTOR signaling pathway.