Transcriptomic analysis of lung tissues after hUC-MSCs and FTY720 treatment of lipopolysaccharide-induced acute lung injury in mouse models

Abstract

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) refer to acute and progressive hypoxic respiratory failure caused by non-cardiogenic factors, which is a common condition occurring in critically ill patients with widespread pulmonary inflammation. Use of a single medication or target cannot treat ALI/ARDS. Mesenchymal stem cells (MSCs) and FTY720, as an analogue of sphingosine-1-phosphate (S1P), can mitigate lipopolysaccharide (LPS)-induced inflammatory lung injury.In this investigation, the clinical efficacy of MSCs alone, FTY720 alone, and a MSC and FTY720 combination in the treatment of LPS-induced lung injury was evaluated in mouse models. The experimental results demonstrated that both MSCs and FTY720 alleviate lung injuries in mice. The combined application of MSCs and FTY720 yielded higher clinical efficacy in mitigating lung injuries compared with use of MSCs or FTY720 alone. Transcriptomic analysis was performed using an Agilent gene expression chip. By analyzing the differences in gene expression of lung tissues between treated and non-treated ALI/ARDS mice, Gene Ontology and Pathway terms related to ALI/ARDS treatment were identified. Moreover, the target genes which might play a pivotal role in the treatment of ALI/ARDS were also detected, thus providing a theoretical basis for multi-target or multi-drug combined treatment of ALI/ARDS and lay a solid foundation for clinical treatment of ALI/ARDS.