Long non-coding RNA gas5 and intestinal mmp2 and mmp9 expression: A translational study in pediatric patients with IBD

Marianna Lucafò, Letizia Pugnetti, Matteo Bramuzzo, Debora Curci, Alessia Di Silvestre, Annalisa Marcuzzi, Alberta Bergamo, Stefano Martelossi, Vincenzo Villanacci, Anna Bozzola, Moris Cadei, Sara De Iudicibus, Giuliana Decorti, Gabriele Stocco

Research output: Contribution to journalArticle

Abstract

Background: The long non-coding RNA (lncRNA) growth arrest–specific transcript 5 (GAS5) seems to be involved in the regulation of mediators of tissue injury, in particular matrix metalloproteinases (MMPs), implicated in the pathogenesis of inflammatory bowel disease (IBD). We investigated the role of GAS5 in regulating MMP2 and MMP9 expression in pediatric patients with IBD and in vitro. Methods: In total, 25 IBD patients were enrolled: For each patient paired inflamed and non-inflamed biopsies were collected. RNA was extracted and GAS5, MMP2, and MMP9 were quantified by TaqMan assay. The expression of GAS5 and MMPs was also determined in the human monocytic THP1 cells differentiated into macrophages and stimulated with lipopolysaccharide (LPS). The function of GAS5 was assessed by overexpressing the lncRNA and evaluating the MMPs levels. Results: Real-time PCR results demonstrated a downregulation of GAS5 and an upregulation of both MMPs in inflamed tissues. In vitro data confirmed the trend observed in patients for the three genes: The stimulation with LPS promoted a downregulation of GAS5 while an increase of MMPs was observed. Overexpression experiments showed that higher levels of GAS5 lead to a decrease of both enzymes. Conclusion: These results provide new information about the role of GAS5 in IBD: The lncRNA could mediate tissue damage by modulating the expression of MMPs.

Original languageEnglish
Article number5280
JournalInternational Journal of Molecular Sciences
Volume20
Issue number21
DOIs
Publication statusPublished - Nov 1 2019

Keywords

  • GAS5
  • Inflammatory bowel disease
  • Long non-coding-RNA
  • MMP2
  • MMP9

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Lucafò, M., Pugnetti, L., Bramuzzo, M., Curci, D., Di Silvestre, A., Marcuzzi, A., Bergamo, A., Martelossi, S., Villanacci, V., Bozzola, A., Cadei, M., De Iudicibus, S., Decorti, G., & Stocco, G. (2019). Long non-coding RNA gas5 and intestinal mmp2 and mmp9 expression: A translational study in pediatric patients with IBD. International Journal of Molecular Sciences, 20(21), [5280]. https://doi.org/10.3390/ijms20215280