Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD
Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD
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DOI：
10.3390/ijms20215280
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Stocco, Gabriele
中科院分区：
文献类型：
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作者：
Lucafo, Marianna;Pugnetti, Letizia;Stocco, Gabriele
背景：长链非编码RNA （lncRNA）生长抑制特异性转录物5 （GAS5）似乎参与了组织损伤介质的调节，特别是与炎症性肠病（IBD）发病有关的基质金属蛋白酶（MMPs）。我们在IBD患儿和体外研究了GAS5在调节MMP2和MMP9表达中的作用。方法：共纳入25例IBD患者：对每位患者收集配对的炎症和非炎症活检。提取RNA，采用TaqMan法定量测定GAS5、MMP2、MMP9。在分化为巨噬细胞并经脂多糖刺激的人单核THP1细胞中，测定GAS5和MMPs的表达。通过过表达lncRNA和评估MMPs水平来评估GAS5的功能。结果：Real-time PCR结果显示炎症组织中GAS5下调，两种MMPs上调。体外数据证实了在患者中观察到的三个基因的趋势：LPS刺激促进了GAS5的下调，同时观察到MMPs的增加。过表达实验表明，高水平的GAS5会导致这两种酶的减少。结论：这些结果为GAS5在IBD中的作用提供了新的信息：lncRNA可能通过调节MMPs的表达介导组织损伤。
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.