Diarrhea-predominant irritable bowel syndrome (IBS-D) is a prevalent gastrointestinal disorder with a high incidence in children. The role of long non-coding RNAs (lncRNAs) in gastrointestinal diseases has been previously highlighted. Nevertheless, the underlying regulatory mechanism of lncRNA X inactivate-specific transcript (XIST) in IBS-D requires further studies. Thus, the present study was conducted with the main objective of elucidating the underlying mechanism of lncRNA XIST in visceral hypersensitivity in IBS-D. An in vivo mouse model of IBS-D was constructed via rectal perfusion of acetic acid. Next, in order to evaluate the effect of lncRNA XIST on the development of visceral hypersensitivity in IBS-D, different vector plasmids were injected into mice along with rectal mucosal epithelial cells, followed by the measurement of abdominal withdrawal reflex (AWR) score, counts of peristaltic wave, abdominal wall contraction and defecation particles. Furthermore, luciferase reporter assay, FISH, RIP and ChIP assays were conducted to determine the interactions between lncRNA XIST and SERT. Subsequently, MS-PCR was adopted to test the methylation level of SERT promoter. 5-hydroxytrytophan (HT) content in rectal tissues was detected using immunohistochemistry. The IBS-D mouse models presented with a high expression of lncRNA XIST along with low expression of SERT. LncRNA XIST was observed to recruit methylase DNMT1, DNMT3A and DNMT3B to promote SERT promoter methylation, reducing its expression. Restoration of lncRNA XIST resulted in increased AWR score, counts of peristaltic wave, abdominal wall contraction and defecation particles along with stimulated 5-HT expression and SERT methylation level, while downregulation of lncRNA XIST reversed these effects. In conclusion, the key findings from our study indicated that lncRNA XIST acts as a regulator in 5-HT-induced visceral hypersensitivity in mice with IBS-D, providing a new insight into the regulatory effect of lncRNA XIST and its epigenetic diagnostic and therapeutic properties in IBS-D.

腹泻型肠易激综合征（IBS-D）是一种常见的胃肠道疾病，在儿童中发病率很高。长链非编码 RNA (lncRNAs) 在胃肠道疾病中的作用先前已被强调。然而，IBS-D 中 lncRNA X 失活特异性转录本 (XIST) 的潜在调控机制需要进一步研究。因此，本研究的主要目的是阐明 lncRNA XIST 在 IBS-D 内脏超敏反应中的潜在机制。的体内IBS-d的小鼠模型构建通过醋酸直肠灌注。接下来，为了评估 lncRNA XIST 对 IBS-D 内脏超敏反应发展的影响，将不同的载体质粒与直肠粘膜上皮细胞一起注射到小鼠体内，然后测量腹部退缩反射（AWR）评分，计数蠕动波、腹壁收缩和排便颗粒。此外，还进行了荧光素酶报告基因检测、FISH、RIP 和 ChIP 检测，以确定 lncRNA XIST 和 SERT 之间的相互作用。随后，采用MS-PCR检测SERT启动子的甲基化水平。使用免疫组织化学检测直肠组织中的 5-羟色氨酸 (HT) 含量。IBS-D 小鼠模型表现出 lncRNA XIST 的高表达和 SERT 的低表达。观察到 LncRNA XIST 募集甲基化酶 DNMT1、DNMT3A 和 DNMT3B 以促进 SERT 启动子甲基化，降低其表达。lncRNA XIST 的恢复导致 AWR 评分、蠕动波计数、腹壁收缩和排便颗粒增加，同时刺激 5-HT 表达和 SERT 甲基化水平，而 lncRNA XIST 的下调则逆转了这些影响。总之，我们研究的主要发现表明 lncRNA XIST 在 5-HT 诱导的 IBS-D 小鼠内脏超敏反应中起调节作用，为 lncRNA XIST 的调节作用及其表观遗传诊断和治疗特性提供了新的见解在 IBS-D 中。蠕动波、腹壁收缩和排便颗粒的计数以及刺激的 5-HT 表达和 SERT 甲基化水平，而 lncRNA XIST 的下调则逆转了这些影响。总之，我们研究的主要发现表明，lncRNA XIST 在 5-HT 诱导的 IBS-D 小鼠内脏超敏反应中起调节作用，为 lncRNA XIST 的调节作用及其表观遗传诊断和治疗特性提供了新的见解在 IBS-D 中。蠕动波、腹壁收缩和排便颗粒的计数以及刺激的 5-HT 表达和 SERT 甲基化水平，而 lncRNA XIST 的下调则逆转了这些影响。总之，我们研究的主要发现表明，lncRNA XIST 在 5-HT 诱导的 IBS-D 小鼠内脏超敏反应中起调节作用，为 lncRNA XIST 的调节作用及其表观遗传诊断和治疗特性提供了新的见解在 IBS-D 中。