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

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 o...

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Autores principales: Lucafò, Marianna, Pugnetti, Letizia, Bramuzzo, Matteo, Curci, Debora, Di Silvestre, Alessia, Marcuzzi, Annalisa, Bergamo, Alberta, Martelossi, Stefano, Villanacci, Vincenzo, Bozzola, Anna, Cadei, Moris, De Iudicibus, Sara, Decorti, Giuliana, Stocco, Gabriele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862115/
https://www.ncbi.nlm.nih.gov/pubmed/31652976
http://dx.doi.org/10.3390/ijms20215280
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author Lucafò, Marianna
Pugnetti, Letizia
Bramuzzo, Matteo
Curci, Debora
Di Silvestre, Alessia
Marcuzzi, Annalisa
Bergamo, Alberta
Martelossi, Stefano
Villanacci, Vincenzo
Bozzola, Anna
Cadei, Moris
De Iudicibus, Sara
Decorti, Giuliana
Stocco, Gabriele
author_facet Lucafò, Marianna
Pugnetti, Letizia
Bramuzzo, Matteo
Curci, Debora
Di Silvestre, Alessia
Marcuzzi, Annalisa
Bergamo, Alberta
Martelossi, Stefano
Villanacci, Vincenzo
Bozzola, Anna
Cadei, Moris
De Iudicibus, Sara
Decorti, Giuliana
Stocco, Gabriele
author_sort Lucafò, Marianna
collection PubMed
description 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.
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spelling pubmed-68621152019-12-05 Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD Lucafò, Marianna Pugnetti, Letizia Bramuzzo, Matteo Curci, Debora Di Silvestre, Alessia Marcuzzi, Annalisa Bergamo, Alberta Martelossi, Stefano Villanacci, Vincenzo Bozzola, Anna Cadei, Moris De Iudicibus, Sara Decorti, Giuliana Stocco, Gabriele Int J Mol Sci Article 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. MDPI 2019-10-24 /pmc/articles/PMC6862115/ /pubmed/31652976 http://dx.doi.org/10.3390/ijms20215280 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lucafò, Marianna
Pugnetti, Letizia
Bramuzzo, Matteo
Curci, Debora
Di Silvestre, Alessia
Marcuzzi, Annalisa
Bergamo, Alberta
Martelossi, Stefano
Villanacci, Vincenzo
Bozzola, Anna
Cadei, Moris
De Iudicibus, Sara
Decorti, Giuliana
Stocco, Gabriele
Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD
title Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD
title_full Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD
title_fullStr Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD
title_full_unstemmed Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD
title_short Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD
title_sort long non-coding rna gas5 and intestinal mmp2 and mmp9 expression: a translational study in pediatric patients with ibd
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862115/
https://www.ncbi.nlm.nih.gov/pubmed/31652976
http://dx.doi.org/10.3390/ijms20215280
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