Neat1-miRNA204-5p-PI3K-AKT axis as a potential mechanism for photodynamic therapy treated colitis in mice

Kunpeng Wang, Zijian Zhang, Kai Liu, Xin Yang, Heng Zou, Jiangjiao Zhou, Xiongying Miao, Wei Chen, Li Xiong*, Yu Wen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Background: Inflammatory bowel disease (IBD) is a group of inflammatory conditions characterized by chronic inflammation of the gastrointestinal (GI) tract. Recent preclinical and clinical studies have shown the therapeutic value of photodynamic therapy with low doses of photosensitizer and/or light in colitis treatment, but the detailed mechanism is unclear. Methods: We examined 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy (PDT) in dextran sulfate sodium (DSS)-induced colitis in mice. Endoscopic and macroscopic observations as well as the Disease Activity Index score (DAI) was used to monitor the disease. Cytokine expression was measured by quantitative RT-PCR analysis to evaluate the efficacy of PDT. We applied the Clariom™ D bioinformatics analysis to investigate the differentially expressed genes after PDT. Finally, we used quantitative RT-PCR analysis and Western blotting to validate the targets of differentially expressed genes. Results: 5-ALA-PDT improved the DAI score and decreased the expression of various inflammatory cytokines. The Clariom™ D bioinformatics analysis identified 2043 diff;erentially expressed genes (702 up-regulated and 1341 down-regulated). We confirmed the down-regulation of lncRNA-Neat1, lncRNA-Snhg5 and lncRNA-Gm9926 and the up-regulation of miRNA-204-5p, miRNA-218-5p, miRNA-200a-3p and miRNA-466h-5p. Additionally, the decreased expression level of the AKT3, p-AKT3, PI3K, p-PI3K protein were confirmed. Conclusions: This study provides in vivo comprehensive lncRNA and miRNA microarray analysis after 5-ALA-PDT treatment in DSS-induced colitis, and it may help to develop novel lncRNA-miRNA-related therapeutic approaches, such as the Neat1-miRNA204-5p-PI3K-AKT axis, to further increase the efficiency of PDT in IBD.

Original languageEnglish
Pages (from-to)349-357
Number of pages9
JournalPhotodiagnosis and Photodynamic Therapy
Volume24
DOIs
Publication statusPublished - Dec 2018
Externally publishedYes

Keywords

  • 5-ALA
  • Inflammatory bowel disease
  • lncRNAs
  • miRNAs
  • Photodynamic therapy

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