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

Biochem Biophys Res Commun. 2020 May 28;526(2):439-446. doi: 10.1016/j.bbrc.2020.03.103. Epub 2020 Mar 27.

Abstract

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.

Keywords: ALI; GDF-15; Lipopolysaccharide; SIRT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / genetics*
  • Acute Lung Injury / prevention & control
  • Animals
  • Apoptosis
  • Cell Line
  • Disease Models, Animal
  • Gene Silencing
  • Growth Differentiation Factor 15 / genetics*
  • Growth Differentiation Factor 15 / therapeutic use
  • Humans
  • Lipopolysaccharides
  • Male
  • Mice, Inbred C57BL
  • Sirtuin 1 / genetics*
  • Up-Regulation*

Substances

  • Gdf15 protein, mouse
  • Growth Differentiation Factor 15
  • Lipopolysaccharides
  • Sirt1 protein, mouse
  • Sirtuin 1