Endocan attenuates LPS-induced alveolar type II cells injury through PI3K/Akt/mTOR pathway.

Abstract

Background: Alveolar type II (AT2) cell injury plays an important role in the pathogenesis of acute lung injury (ALI), but the corresponding treatment options are limited in clinical practice. Endocan has been proved to exert a protective effect in ALI, however, the underlying mechanism remains unclear. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway was found to exhibit beneficial effects in lipopolysaccharide-induced ALI. This study aimed to investigate protective effects of endocan on AT2 cells and the signal pathway in LPS-induced ALI.

Methods: Pulmonary function testing and hematoxylin-eosin staining were employed to evaluate the effects of endocan on the LPS-induced ALI in mice. Transmission electron microscopy (TEM) analysis, immunofluorescence and Western blot were used to assess the AT2 protection of endocan. Mouse lung epithelial cell line 12 (MLE-12) cells were facilitated to observe the activation of PI3K/AKT/mTOR pathway.

Results: Endocan administration effectively ameliorated respiratory parameters in LPS-challenged ALI mice. TEM revealed that endocan treatment preserved AT2 cell integrity and maintained lamellar body ultrastructure compared to the mice injected LPS only. Western blot analysis showed a higher surfactant protein C expression in endocan-treated mice than that of model group. Moreover, the phosph-PI3K, -AKT, -mTOR levels detected by Western blot were significantly observed upregulated after endocan treatment. However, rapamycin, an mTOR inhibitor, abolished the protective effects of endocan against ALI, indicating this pathway may be critical for its action on AT2 cells. In LPS-treated MLE-12 cells, the Western blot analysis further confirmed that rapamycin suppressed endocan-induced activation of the PI3K/AKT/mTOR pathway, thereby attenuating the protective effects of endocan on MLE-12 cells.

Conclusion: Endocan protects AT2 cells against ALI through activating PI3K/AKT/mTOR pathway, suggesting its therapeutic potential for AT2 in patients with ALI.