Defective apoptosis in intestinal and mesenteric adipose tissue of Crohn's disease patients

Cilene Bicca Dias; Marciane Milanski; Mariana Portovedo; Vivian Horita; Maria de Lourdes Setsuko Ayrizono; Núria Planell; Cláudio Saddy Rodrigues Coy; Lício Augusto Velloso; Luciana Rodrigues Meirelles; Raquel Franco Leal

doi:10.1371/journal.pone.0098547

Defective apoptosis in intestinal and mesenteric adipose tissue of Crohn's disease patients

PLoS One. 2014 Jun 2;9(6):e98547. doi: 10.1371/journal.pone.0098547. eCollection 2014.

Affiliations

¹ Coloproctology Unit, Surgery Department, University of Campinas (UNICAMP), Medical School, Sao Paulo, Brazil; Laboratory of Cell Signaling, Internal Medicine Department, University of Campinas (UNICAMP), Medical School, Sao Paulo, Brazil; Doctoral CAPES fellowship, Post graduate Program in Surgery Sciences, Faculty of Medical School, University of Campinas, Sao Paulo, Brazil.
² Laboratory of Cell Signaling, Internal Medicine Department, University of Campinas (UNICAMP), Medical School, Sao Paulo, Brazil.
³ Department of Pathology, University of Campinas (UNICAMP), Medical School, Sao Paulo, Brazil.
⁴ Coloproctology Unit, Surgery Department, University of Campinas (UNICAMP), Medical School, Sao Paulo, Brazil.
⁵ Department of Gastroenterology and Bioinformatics Platform, CIBERehd, Barcelona, Spain.
⁶ Coloproctology Unit, Surgery Department, University of Campinas (UNICAMP), Medical School, Sao Paulo, Brazil; Laboratory of Cell Signaling, Internal Medicine Department, University of Campinas (UNICAMP), Medical School, Sao Paulo, Brazil.

Abstract

Background: Crohn's disease (CD) is associated with complex pathogenic pathways involving defects in apoptosis mechanisms. Recently, mesenteric adipose tissue (MAT) has been associated with CD ethiopathology, since adipose thickening is detected close to the affected intestinal area. However, the potential role of altered apoptosis in MAT of CD has not been addressed.

Aims: To evaluate apoptosis in the intestinal mucosa and MAT of patients with CD.

Methods: Samples of intestinal mucosa and MAT from patients with ileocecal CD and from non-inflammatory bowel diseases patients (controls) were studied. Apoptosis was assessed by TUNEL assay and correlated with the adipocytes histological morphometric analysis. The transcriptional and protein analysis of selected genes and proteins related to apoptosis were determined.

Results: TUNEL assay showed fewer apoptotic cells in CD, when compared to the control groups, both in the intestinal mucosa and in MAT. In addition, the number of apoptotic cells (TUNEL) correlated significantly with the area and perimeter of the adipose cells in MAT. Transcriptomic and proteomic analysis reveal a significantly lower transcript and protein levels of Bax in the intestinal mucosa of CD, compared to the controls; low protein levels of Bax were found localized in the lamina propria and not in the epithelium of this tissue. Furthermore, higher level of Bcl-2 and low level of Caspase 3 were seen in the MAT of CD patients.

Conclusion: The defective apoptosis in MAT may explain the singular morphological characteristics of this tissue in CD, which may be implicated in the pathophysiology of the disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / pathology*
Apoptosis*
Case-Control Studies
Crohn Disease / pathology*
Humans
In Situ Nick-End Labeling
Intestines / pathology*
Mesentery / pathology*

Grants and funding

FAPESP (Foundation for Research Support of the Sao Paulo State) for financial support and CAPES-Brazil for research fellowship (C.B. Dias). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.