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CADM1 enhances intestinal barrier function in a rat model of mild inflammatory bowel disease by inhibiting the STAT3 signaling pathway

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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, 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.

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Abbreviations

CADM1 :

Cell adhesion molecule 1

IBS-D :

irritable bowel syndrome with diarrhoea

FWC :

faecal water content

DAO :

diamine oxidase

TNF-α :

tumor necrosis factor-α

IL-6 :

interleukin-6

JAK1 :

Janus kinase 1

GI :

gastrointestinal

IGSF-CAMs :

immunoglobulin superfamily of cell adhesion molecules

SqCCs :

squamous cell carcinomas

DEGs :

differentially expressed genes

SPF :

Specific-pathogen-free

SD :

Sprague-Dawley

PBS :

phosphate buffer saline

AWR :

abdominal withdrawal reflex

FWC :

faecal water content

DMEM :

ulbecco’s modified Eagle’s Medium

51 Cr-EDTA :

51Cr-ethylenediaminetetraacetic acid

sIgA :

secretory immunoglobulin A

EP :

eppendorf

ELISA :

enzyme-linked immunosorbent assay

DAO :

diamine oxidase

HE :

Hematoxylin-eosin

BSA :

bovine serum albumin

SAB :

Staphylococcus aureus bacteremia

DAB :

diaminobenzidine

TNF-α :

tumor necrosis factor-α

OD :

optical density

RT-qPCR :

Reverse transcription quantitative polymerase chain reaction

cDNA :

complementary DNA

GAPDH :

glyceraldehyde-3-phosphate dehydrogenase

JAK1 :

Janus kinase 1

SDS :

sodium dodecyl sulfate

PAGE :

polyacrylamide gel electrophoresis

PVDF :

polyvinylidene fluoride

HRP :

horseradish peroxidase

TBST :

Tris-buffered saline Tween-20

ECL :

enhanced chemiluminescence

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Acknowledgements

We would like to express our sincere appreciation to the reviewers for their helpful comments on this article.

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Authors and Affiliations

  1. Department of Pediatrics, Linyi People’s Hospital, No. 27, Eastern Jiefang Road, Lanshan District, Linyi, 276003, Shandong Province, People’s Republic of China

    Shengtao Sun, Wenlong Liu & Yinfeng Li

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  1. Shengtao Sun
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  2. Wenlong Liu
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Correspondence to Yinfeng Li.

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Sun, S., Liu, W. & Li, Y. CADM1 enhances intestinal barrier function in a rat model of mild inflammatory bowel disease by inhibiting the STAT3 signaling pathway. J Bioenerg Biomembr 52, 343–354 (2020). https://doi.org/10.1007/s10863-020-09850-8

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  • DOI: https://doi.org/10.1007/s10863-020-09850-8

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