Cell adhesion molecule 1 (CADM1) is frequently silenced in lung, prostate, liver, stomach, pancreatic and breast carcinomas and other forms of human carcinomas. However, it is unclear regarding the role of CADM1 in irritable bowel syndrome with diarrhoea (IBS-D) that is the most common gastrointestinal diagnosis and may contribute to impaired intestinal barrier function. The aim of the present study is to explore the potential mechanism of CADM1 in regulating intestinal barrier function in IBS-D. A rat model with IBS-D induced by the combination method of mother-infant separation, acetic acid and restraint stress was initially established. The defecation frequency, faecal water content (FWC), total intestinal permeability, sIgA, endotoxin, D-lactic acid and diamine oxidase (DAO) were then measured. Next, positive expression of CADM1 protein was detected in distal colonic tissue of rats by immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in distal colonic mucosa, CADM1, Janus kinase 1 (JAK1), STAT3, p-JAK1, p-STAT3, Claudin-1and Claudin-2 were evaluated using ELISA, RT-qPCR and western blot analysis. IBS-D rats exhibited low CADM1 expression and activated STAT3 signaling pathway. Overexpression of CADM1 in rats was shown to increase Claudin-1 expression, while decreasing expression of STAT3, Claudin-2, TNF-α and IL-6. In addition, silencing of CADM1 or inhibition of the STAT3 signaling pathway was demonstrated to improve the intestinal barrier function. Our study provides evidence that CADM1 can potentially improve intestinal barrier function in rats with IBS-D by inhibiting the STAT3 signaling pathway.

细胞粘附分子1（CADM1）在肺癌，前列腺癌，肝癌，胃癌，胰腺癌和乳腺癌以及其他形式的人类癌症中经常沉默。然而，关于CADM1在肠易激惹性腹泻（IBS-D）中的作用尚不清楚，IBS-D是最常见的胃肠道诊断，可能导致肠屏障功能受损。本研究的目的是探讨CADM1调节IBS-D肠屏障功能的潜在机制。初步建立了母婴分离，醋酸和束缚应激相结合的IBS-D大鼠模型。然后测量排便频率，粪便含水量（FWC），总肠通透性，sIgA，内毒素，D-乳酸和二胺氧化酶（DAO）。下一个，免疫组化法检测大鼠远端结肠组织中CADM1蛋白的阳性表达。肿瘤坏死因子-α（TNF-α）和白细胞介素6（IL-6）在结肠远端黏膜，CADM1，Janus激酶1（JAK1），STAT3，p-JAK1，p-STAT3，Claudin-1和Claudin中的表达-2使用ELISA，RT-qPCR和Western blot分析进行评估。IBS-D大鼠表现出低CADM1表达和激活的STAT3信号通路。在大鼠中，CADM1的过度表达可提高Claudin-1的表达，同时降低STAT3，Claudin-2，TNF-α和IL-6的表达。此外，证明了沉默CADM1或抑制STAT3信号通路可改善肠屏障功能。