CADM1 enhances intestinal barrier function in a rat model of mild inflammatory bowel disease by inhibiting the STAT3 sig
- PDF / 1,258,728 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 79 Downloads / 158 Views
CADM1 enhances intestinal barrier function in a rat model of mild inflammatory bowel disease by inhibiting the STAT3 signaling pathway Shengtao Sun 1 & Wenlong Liu 1 & Yinfeng Li 1 Received: 8 May 2020 / Accepted: 18 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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, Dlactic 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. Keywords CADM1 . STAT3 signaling pathway . Intestinal barrier function . Irritable bowel syndrome with diarrhoea
Introduction Irritable bowel syndrome (IBS) is a disease of the gastrointestinal (GI) tract (Lovell and Ford 2012). Individuals with PIIBS are a clinically distinct subgroup characterized by diarrheal symptoms, less psychiatric illness, and increased serotonin-containing EC cells compared to those with nonPI-IBS (Dunlop et al. 2003; Barbara et al. 2004). IBS is associated with a series of multifactorial environmental factors, including acute GI infections, food intolerance and background genetic predisposition (Cremonini and Talley 2005). It has been confirmed that the intestinal permeability increases before the development of colonic disease; thereby, the agents * Yinfeng Li [email protected] 1
Department of Pediatrics, Linyi People’s Hospital, No. 27, Eastern Jiefang Road, Lanshan District, Linyi 276003, Shandong Province, People’s Republic of China
that suppress intestinal barrier dysfunction and intestinal permeability may be beneficial for the treatm
Data Loading...
