Department of Pediatrics, Linyi People's Hospital, No. 27, Eastern Jiefang Road, Lanshan District, Linyi, 276003, Shandong Province, People's Republic of China.
J Bioenerg Biomembr. 2020 Oct;52(5):343-354. doi: 10.1007/s10863-020-09850-8. Epub 2020 Sep 14.
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.
细胞黏附分子 1（CADM1）在肺癌、前列腺癌、肝癌、胃癌、胰腺癌和乳腺癌等多种人类癌症中常被沉默。然而，CADM1 在腹泻型肠易激综合征（IBS-D）中的作用尚不清楚，IBS-D 是最常见的胃肠道诊断，可能导致肠道屏障功能受损。本研究旨在探讨 CADM1 调节 IBS-D 肠道屏障功能的潜在机制。首先采用母婴分离、醋酸和束缚应激联合的方法建立 IBS-D 大鼠模型，然后测量排便频率、粪便含水量（FWC）、总肠道通透性、sIgA、内毒素、D-乳酸和二胺氧化酶（DAO）。接下来，通过免疫组织化学检测大鼠远端结肠组织中 CADM1 蛋白的阳性表达。采用 ELISA、RT-qPCR 和 Western blot 分析检测大鼠远端结肠黏膜中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）、CADM1、Janus 激酶 1（JAK1）、STAT3、p-JAK1、p-STAT3、Claudin-1 和 Claudin-2 的表达。IBS-D 大鼠表现出 CADM1 表达降低和 STAT3 信号通路激活。CADM1 在大鼠中的过表达增加 Claudin-1 的表达，同时降低 STAT3、Claudin-2、TNF-α和 IL-6 的表达。此外，沉默 CADM1 或抑制 STAT3 信号通路可改善肠道屏障功能。本研究表明，CADM1 可能通过抑制 STAT3 信号通路来改善 IBS-D 大鼠的肠道屏障功能。
