Transcriptional and Molecular Pathways Activated in Mesenteric Adipose Tissue and Intestinal Mucosa of Crohn's Disease Patients.

Andressa Coope,Michel Gardere Camargo,João José Fagundes,Raquel Franco Leal,Cilene Bicca Dias,Lívia Bitencourt Pascoal,Mariana Portovedo,Núria Planell,Francesca Aparecida Ramos Da Silva,Maria De Lourdes Setsuko Ayrizono,Marciane Milanski,José Diego Botezelli

doi:10.1155/2017/7646859

Abstract

Crohn's disease (CD) is a chronic inflammatory disorder, characterized by cytokine imbalance and transcription signaling pathways activation. In addition, the increase of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Therefore, we evaluated the transcription signaling pathways and cytokines expression in intestinal mucosa and MAT of active CD patients. Ten patients with ileocecal CD and eight with noninflammatory diseases were studied. The biopsies of intestinal mucosa and MAT were snap-frozen and protein expression was determined by immunoblotting. RNA levels were measured by qPCR. The pIkB/IkB ratio and TNFα level were significantly higher in intestinal mucosa of CD when compared to controls. However, STAT1 expression was similar between intestinal mucosa of CD and controls. Considering the MAT, the pIkB/IkB ratio was significantly lower and the anti-inflammatory cytokine IL10 was significantly higher in CD when compared to controls. Finally, the protein content of pSTAT1 was higher in MAT of CD compared to controls. These findings reinforce the predominance of the proinflammatory NF-kB pathway in CD intestinal mucosa. For the first time, we showed the activation of STAT1 pathway in MAT of CD patients, which may help to understand the physiopathology of this immune mediated disease.

Highlights

Crohn’s disease (CD) is characterized by mucosal immune cell activation and cytokine imbalance
We demonstrated that the area and the perimeter of the mesenteric adipose tissue (MAT) were lower (Figure 1(d)) in CD patients when compared to the control group (Figure 1(c))
The predominance of nuclear factor kB (NF-kB) activation in CD and STAT1 activation in ulcerative colitis (UC) has been reported in the literature [9, 10, 17]

Summary

Introduction

Crohn’s disease (CD) is characterized by mucosal immune cell activation and cytokine imbalance. Some members of the signal transducer and activator of transcription (STAT) family have been involved in this process. All the transcription factors translocate into the nucleus and interact with conserved regulatory DNA sequences resulting in the transcription of genes like chemokines, cytokines, receptors, signaling regulatory genes, among others. Those molecules have been studied in several gastrointestinal disorders. The increase of the MAT is a common feature of the disease and may involve the small and large bowels; this tissue may represent a relevant role in the pathogenesis of CD [3, 4].

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Methods

Conclusion