GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling Pathway

Abstract EN

The reduction of pulmonary surfactant (PS) is essential for decreased pulmonary compliance and edema in acute lung injury (ALI).

Thyroid transcription factor-1 (TTF-1) plays a major role in the regulation of surfactant protein-A (SP-A), the most abundant protein component of PS.

Simultaneously, the glucagon-like peptide-1 (GLP-1) analogue can enhance SP-A expression in the lung.

However, the underlying mechanism is still unknown.

The purpose of this study was to explore whether liraglutide, a GLP-1 analogue, upregulates SP-A expression through the TTF-1 signaling pathway in ALI.

In vivo, a murine model of ALI was induced by lipopolysaccharide (LPS).

Pulmonary inflammation, edema, insulin level, ultrastructural changes in type II alveolar epithelial (ATII) cells, and SP-A and TTF-1 expression were analyzed.

In vitro, rat ATII cells were obtained.

SP-A and TTF-1 expression in cells was measured.

ShRNA-TTF-1 transfection was performed to knock down TTF-1 expression.

Our data showed that LPS-induced lung injury and increase in insulin level, and LPS-induced reduction of SP-A and TTF-1 expression in both the lung and cells, were significantly compromised by liraglutide.

Furthermore, we also found that these effects of liraglutide were markedly blunted by shRNA-TTF-1.

Taken together, our findings suggest that liraglutide enhances SP-A expression in ATII cells and attenuates pulmonary inflammation in LPS-induced ALI, most likely through the TTF-1 signaling pathway.