APELIN-13 AMELIORATES LPS-INDUCED ENDOTHELIAL-TO-MESENCHYMAL TRANSITION AND POST–ACUTE LUNG INJURY PULMONARY FIBROSIS BY SUPPRESSING TRANSFORMING GROWTH FACTOR-Β1 SIGNALING

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 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 analysed 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 analyse the protective effect and underlying mechanism of apelin-13. Mice were treated with apelin-13 by intraperitoneal injection, and human pulmonary microvascular endothelial cells (HPMECs) 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-SMA expression and collagen deposition. LPS also stimulated the production of transforming growth factor-1 (TGF-β1) and activated the Smad signalling 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 signalling.