Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: International Journal of Molecular Sciences
• Subjects: inflammatory bowel disease; long non-coding-rna; <i>gas5</i>; <i>mmp2</i>; <i>mmp9</i>
• Online Access: https://www.mdpi.com/1422-0067/20/21/5280

Background: The long non-coding RNA (lncRNA) growth arrest&#8722;specific transcript 5 (<i>GAS5</i>) 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 <i>GAS5</i> in regulating <i>MMP2</i> and <i>MMP9</i> 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 <i>GAS5</i>, <i>MMP2</i>, and <i>MMP9</i> were quantified by TaqMan assay. The expression of <i>GAS5</i> and MMPs was also determined in the human monocytic THP1 cells differentiated into macrophages and stimulated with lipopolysaccharide (LPS). The function of <i>GAS5</i> was assessed by overexpressing the lncRNA and evaluating the MMPs levels. Results: Real-time PCR results demonstrated a downregulation of <i>GAS5</i> 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 <i>GAS5</i> while an increase of MMPs was observed. Overexpression experiments showed that higher levels of <i>GAS5</i> lead to a decrease of both enzymes. Conclusion: These results provide new information about the role of <i>GAS5</i> in IBD: The lncRNA could mediate tissue damage by modulating the expression of MMPs.