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Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with
Marianna Lucafò1, Letizia Pugnetti2, Matteo Bramuzzo3
1Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", 34137 Trieste, Italy. marianna.lucafo@burlo.trieste.it.
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.
Insights
Growth arrest-specific transcript 5 (GAS5) long non-coding RNA is downregulated in inflammatory bowel disease (IBD) tissues. Lower GAS5 levels correlate with increased matrix metalloproteinases (MMPs), suggesting GAS5 may protect against IBD-related tissue damage.
Area of Science:
- Molecular Biology
- Genetics
- Immunology
Background:
- The long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) is implicated in regulating matrix metalloproteinases (MMPs), key mediators of tissue injury.
- Matrix metalloproteinases (MMPs) play a significant role in the pathogenesis of inflammatory bowel disease (IBD).
Purpose of the Study:
- To investigate the role of GAS5 in regulating MMP2 and MMP9 expression in pediatric IBD patients.
- To explore the in vitro relationship between GAS5, MMP2, and MMP9 in a cellular model of inflammation.
Main Methods:
- Quantification of GAS5, MMP2, and MMP9 expression in paired inflamed and non-inflamed biopsies from 25 pediatric IBD patients using TaqMan assays.
- Determination of gene expression in lipopolysaccharide (LPS)-stimulated human monocytic THP1 cells differentiated into macrophages.
- Assessment of GAS5 function through overexpression studies and subsequent evaluation of MMP levels.
Main Results:
- A significant downregulation of GAS5 and upregulation of MMP2 and MMP9 were observed in inflamed IBD tissues compared to non-inflamed tissues.
- In vitro, LPS stimulation led to decreased GAS5 expression and increased MMP expression, mirroring the in vivo findings.
- Overexpression of GAS5 resulted in a notable decrease in both MMP2 and MMP9 levels.
Conclusions:
- GAS5 expression is reduced in inflamed tissues of pediatric IBD patients.
- GAS5 negatively regulates the expression of MMP2 and MMP9.
- GAS5 may act as a protective factor against tissue damage in IBD by modulating MMP expression.
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