Abstract
Understanding the molecular mechanisms inducing and regulating epithelial-to-mesenchymal transition (EMT) upon chronic intestinal inflammation is critical for understanding the exact pathomechanism of inflammatory bowel disease (IBD). The aim of this study was to determine the expression profile of TAM family receptors in an inflamed colon. For this, we used a rat model of experimental colitis and also collected samples from colons of IBD patients. Samples were taken from both inflamed and uninflamed regions of the same colon; the total RNA was isolated, and the mRNA and microRNA expressions were monitored. We have determined that AXL is highly induced in active-inflamed colon, which is accompanied with reduced expression of AXL-regulating microRNAs. In addition, the expression of genes responsible for inducing or maintaining mesenchymal phenotype, such as SNAI1, ZEB2, VIM, MMP9, and HIF1α, were all significantly induced in the active-inflamed colon of IBD patients while the epithelial marker E-cadherin (CDH1) was downregulated. We also show that, in vitro, monocytic and colonic epithelial cells increase the expression of AXL in response to LPS or TNFα stimuli, respectively. In summary, we identified several interacting genes and microRNAs with mutually exclusive expression pattern in active-inflamed colon of IBD patients. Our results shed light onto a possible AXL- and microRNA-mediated regulation influencing epithelial-to-mesenchymal transition in IBD.
Highlights
Inflammatory bowel disease (IBD) is a group of multifactorial disorders characterized by chronic inflammation along the digestive tract, and in combination with lifestyle, it is associated with genetic and environmental factors [1, 2]
Male Wistar rats were randomly divided into two groups: the first group served as control and the second group was induced by trinitrobenzene sulphonic acid (TNBS) based on the method described by Morris et al [33]. 72 hours after the treatment, all animals were sacrificed, and distal colons were removed
Our present study demonstrates that the epithelial-tomesenchymal transition is triggered in IBD patients
Summary
Inflammatory bowel disease (IBD) is a group of multifactorial disorders characterized by chronic inflammation along the digestive tract, and in combination with lifestyle, it is associated with genetic and environmental factors [1, 2]. IBD comprises two main types of intestinal inflammation: Crohn’s disease (CD) and ulcerative colitis (UC). As a life-long disease, the main symptoms of IBD—such as abdominal pain, diarrhea, and fatigue—are highly reducing the quality of life; in addition, prolonged inflammation increases the risk of colitisassociated colorectal cancer (CRC) [5]. Defects in immune tolerance in the gut against commensal microorganisms or insufficient negative immune regulation may Mediators of Inflammation cause robust inflammation leading to colitis-associated colorectal cancer [8]
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