The splicing factor SRSF1 stabilizes the mRNA of TSLP to enhance acute lung injury

Abstract

Acute lung injury (ALI) is a severe disease with a high rate of morbidity and mortality, characterized by excessive and uncontrolled inflammatory response in lung. Recent studies demonstrated that serine arginine-rich splicing factor 1 (SRSF1) is involved in inflammation. However, whether SRSF1 modulates ALI remains to be determined. In this study, we established an ALI mouse model that induced by lipopolysaccharide (LPS), with or without the treatment of SRSF1 antibody. Our result showed that SRSF1 expression was elevated in LPS-induced ALI. Importantly, treatment with SRSF1 antibody notably ameliorated ALI in mice, as determined by reduction in lung W/D ratios, histopathological changes, lung inflammation and TSLP expression. Besides, exposure of human alveolar epithelial A549 cells to LPS enhanced the expression of both SRSF1 and TSLP, while knockdown or overexpression of SRSF1 significantly lowered or upregulated the expression of TSLP induced by LPS. Interestingly, the expression of SRSF1 and TSLP showed a positive correlation in normal human lung tissues. Mechanistically, we found that SRSF1 directly bound with the mRNA of TSLP and may exert its function by stabilizing the mRNA of TSLP in LPS-induced ALI. Therefore, our results indicated that SRSF1 may be an important contributor in lung inflammation of LPS-induced ALI and SRSF1 signaling blocking may serve as a potential treatment of ALI.