The pathophysiology of
acute respiratory distress syndrome (ARDS) involves
cytokine storms, alveolar-capillary barrier destruction, and fibrotic progression. Pulmonary interstitial
fibrosis is an important factor affecting the prognosis of ARDS patients. Endothelial-to-mesenchymal transition (EndMT) plays an important role in the development of fibrotic diseases, and the occurrence of EndMT has been observed in experimental models of LPS-induced
acute lung injury (ALI).
Apelin is an endogenous active
polypeptide that plays an important role in maintaining endothelial cell homeostasis and inhibiting fibrotic progression in various diseases. However, whether
apelin attenuates EndMT in ALI and post-ALI
pulmonary fibrosis remains unclear. We analyzed the serum levels of
apelin-13 in patients with
sepsis-associated ARDS to examine its possible clinical value. A murine model of LPS-induced
pulmonary fibrosis and an LPS-challenged endothelial cell injury model were used to analyze the protective effect and underlying mechanism of
apelin-13. Mice were treated with
apelin-13 by i.p. injection, and human pulmonary microvascular endothelial cells were incubated with
apelin-13 in vitro . We found that the circulating
apelin-13 levels were significantly elevated in
sepsis-associated ARDS patients compared with healthy controls. Our study also confirmed that LPS induced EndMT progression and
pulmonary fibrosis, which were characterized by decreased CD31 expression and increased α-smooth muscle actin expression and
collagen deposition. LPS also stimulated the production of
transforming growth factor β1 and activated the Smad signaling pathway. However,
apelin-13 treatment significantly attenuated these changes. Our findings suggest that
apelin-13 may be a novel
biomarker in patients with
sepsis-associated ARDS. These results demonstrate that
apelin-13 ameliorates LPS-induced EndMT and post-ALI
pulmonary fibrosis by suppressing
transforming growth factor β1 signaling.