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

Int Immunopharmacol. 2019 Jun:71:68-75. doi: 10.1016/j.intimp.2019.03.017. Epub 2019 Mar 14.

Abstract

Acute lung injury (ALI), a persistent lung inflammatory response syndrome, may evolve into acute respiratory distress syndrome (ARDS). Characterized by rapid onset, critical features, and a complex etiology, ALI remains a challenging critical respiratory disease. Recently, mesenchymal stem cells (MSCs) have provided a new solution for the treatment of ALI. We built a lipopolysaccharide (LPS)-induced ALI model in mice. After treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs), FTY720, or a combination of hUC-MSCs and FTY207, the lung inflammatory response was apparently attenuated. To understand the mechanism underlying MSCs treatment of ALI at the genetic level, significant differentially expressed long non-coding RNAs (lncRNAs) between the treatment and model groups were analyzed using microarray technology. Moreover, genetic gene prediction, gene ontology (GO) analysis, pathway analysis, and transcription factor (TF) prediction were carried out. The results showed that a total of 66 lncRNAs were differentially expressed in all three treatment groups, including 8 up-regulated and 58 down-regulated lncRNAs. LncRNA A_30_P01029806 and A_30_P01029194, which were down-regulated, were involved in the signaling pathways closely related to ALI. Through further TF analysis, we identified several significant TFs which lay a foundation for revealing the mechanism underlying lncRNAs treatment of ALI. LncRNA A_30_P01029806 and A_30_P01029194 may serve as candidate biomarkers in the diagnosis and treatment of ALI.

Keywords: Acute lung injury (ALI); Long non-coding RNA (lncRNAs); Pathway analysis; Transcription factor; hUC-MSCs.

MeSH terms

  • Acute Lung Injury / therapy*
  • Animals
  • Combined Modality Therapy
  • Disease Models, Animal
  • Fingolimod Hydrochloride / therapeutic use*
  • Gene Expression Regulation
  • Gene Ontology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lipopolysaccharides / immunology
  • Lung / physiology*
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Pneumonia / immunology
  • Pneumonia / therapy*
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • Umbilical Cord / pathology

Substances

  • Immunosuppressive Agents
  • Lipopolysaccharides
  • RNA, Long Noncoding
  • Fingolimod Hydrochloride