Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
PhD School in Science of Reproduction and Development, University of Trieste, 34127 Trieste, Italy.
Int J Mol Sci. 2019 Oct 24;20(21):5280. doi: 10.3390/ijms20215280.
The long non-coding RNA (lncRNA) growth arrest-specific transcript 5 () 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 in regulating and expression in pediatric patients with IBD and in vitro.
In total, 25 IBD patients were enrolled: For each patient paired inflamed and non-inflamed biopsies were collected. RNA was extracted and , , and were quantified by TaqMan assay. The expression of and MMPs was also determined in the human monocytic THP1 cells differentiated into macrophages and stimulated with lipopolysaccharide (LPS). The function of was assessed by overexpressing the lncRNA and evaluating the MMPs levels.
Real-time PCR results demonstrated a downregulation of 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 while an increase of MMPs was observed. Overexpression experiments showed that higher levels of lead to a decrease of both enzymes.
These results provide new information about the role of in IBD: The lncRNA could mediate tissue damage by modulating the expression of MMPs.
长非编码 RNA(lncRNA)生长停滞特异性转录物 5()似乎参与了组织损伤介质的调节,特别是基质金属蛋白酶(MMPs),这些介质与炎症性肠病(IBD)的发病机制有关。我们研究了在小儿 IBD 患者中和体外中调节和表达的作用。
总共纳入了 25 名 IBD 患者:每位患者均采集了配对的炎症和非炎症活检组织。提取 RNA,通过 TaqMan 检测法定量检测、、和。还在人类单核细胞 THP1 细胞分化为巨噬细胞并用脂多糖(LPS)刺激后,确定和 MMPs 的表达。通过过表达 lncRNA 并评估 MMPs 水平来评估的功能。
实时 PCR 结果表明,在炎症组织中下调和上调两种 MMPs。体外数据证实了患者三种基因的观察趋势:LPS 刺激促进下调,而观察到 MMPs 的增加。过表达实验表明,水平升高会导致两种酶的减少。
这些结果提供了关于在 IBD 中作用的新信息:lncRNA 可以通过调节 MMPs 的表达来介导组织损伤。