Search

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. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the gene- and microRNA-expression profile contributing to epithelial to mesenchymal transition in a rat model of experimental colitis. For this, inflammation was induced by injecting 2,4,6-trinitrobenzene sulphonic acid to the colon of male Wistar rats. Samples were taken from both inflamed and uninflamed regions of the same colon, total RNA was isolated, and the mRNA and microRNA expressions were monitored. We have determined that the expression of genes responsible for inducing mesenchymal phenotype, such as Egr1, Fgf2, Fgf7, Jak2, Notch2, Hif1α, Zeb2, Mmp9, Lox, and Vim, was all significantly induced in the inflamed regions of the affected colons while the epithelial marker E-cadherin (Cdh1) was downregulated. In contrast, the expression of microRNAs miR-192, miR-143, miR-375, miR-30a, miR-107, and miR-200b responsible for the regulation of the above mentioned genes was significantly downregulated in inflamed colon. Importantly, we detected moderate induction in the expression of five out of six tested microRNAs in the uninflamed regions. In summary, we identified numerous interacting genes and microRNAs with mutually exclusive expression pattern in inflamed regions of colitis-induced rats. These findings suggest that—among others—an important step in the epithelial to mesenchymal transition in experimental colitis is the dysregulated microRNA expression. [ABSTRACT FROM AUTHOR]

Increasing evidence suggest the significance of inflammation in the progression of cancer, for example the development of colorectal cancer in Inflammatory Bowel Disease (IBD) patients. Long-lasting inflammation in the gastrointestinal tract causes serious systemic complications and breaks the homeostasis of the intestine, where the altered expression of regulatory genes and miRNAs trigger malignant transformations. Several steps lead from acute inflammation to malignancies: epithelial-to-mesenchymal transition (EMT) and inhibitory microRNAs (miRNAs) are known factors during multistage carcinogenesis and IBD pathogenesis. In this review, we outline the interactions between EMT components and miRNAs that may affect cancer development during IBD. [ABSTRACT FROM AUTHOR]