GDF-15 prevents lipopolysaccharide-mediated acute lung injury via upregulating SIRT1

Inflammation and oxidative stress were involved in alveolar epithelial cells (AECs) damage and contributed to the progression of acute lung injury (ALI). Growth differentiation factor-15 (GDF-15) was reported to have important roles in pulmonary diseases, yet its role in AECs damage and ALI remains elusive. Herein, we found that GDF-15 was upregulated upon LPS stimulation in murine lungs and human AECs. GDF-15 treatment prevented, whereas Gdf-15 silence aggravated LPS-induced inflammation, oxidative stress and apoptosis. Moreover, we determined that GDF-15 alleviated AECs damage and ALI via upregulating SIRT1, and SIRT1 suppression completely abrogated the beneficial effects of GDF-15 in vivo and in vitro. GDF-15 protected against LPS-triggered AECs damage and ALI via upregulating SIRT1, and GDF-15 might be a valuable therapeutic candidate for treating ALI. (C) 2020 Elsevier Inc. All rights reserved.