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Transcriptional analysis of intestinal mucosa and mesenteric adipose tissue of patients with Crohn's disease

Grant number: 16/01638-7
Support Opportunities:Regular Research Grants
Duration: August 01, 2016 - July 31, 2018
Field of knowledge:Biological Sciences - Immunology - Immunogenetics
Principal Investigator:Raquel Franco Leal
Grantee:Raquel Franco Leal
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated researchers:Licio Augusto Velloso ; Marciane Milanski Ferreira ; Maria de Lourdes Setsuko Ayrizono


Crohn's disease (CD) is a chronic intestinal disorder with a multifactorial etiology, whose incidence has increased during the last three decades. Intestinal involvement is transmural, thus there is possibility of developing fistulas and strictures. The role of mesenteric adipose tissue (MAT) in the development of these complications, as well as, with the disease etiology is not well established. The characteristic macroscopic increase of intestinal MAT near the affected intestinal area, with circumferential involvement of the intestinal loop was noticed since the description of CD, but there are few studies that address this issue. In this study, we intend to evaluate samples of intestinal mucosa and MAT of patients with ileocecal CD, and from control subjects, which were already collected. Transcriptional study will be conducted using RNA-seq analysis, and the genes of interest will be validated in an independent cohort by RT-PCR, immunoblotting and histological study. We will focus mainly on transcripts related to the occurrence of endoplasmic reticulum stress in both the intestinal mucosa and MAT. To achieve this goal, RNA-seq analysis will be performed for samples of 10 patients with ileocecal CD, whose samples of intestinal mucosa (ICD Group) and of MAT were already obtained (ACD); 10 patients without inflammatory bowel disease (control group AC); 10 subjects with normal colonoscopy (control group IC). The validation cohort will comprise over 10 other individuals for each group mentioned above. Thus, this study may identify tissue-specific differences that could be involved in susceptibility to disease, and also may identify potential biomarkers and targets of pharmacological agents, individualizing therapies. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DA SILVA, FRANCESCA APARECIDA RAMOS; PASCOAL, LIVIA BITENCOURT; DOTTI, ISABELLA; SETSUKO AYRIZONO, MARIA DE LOURDES; AGUILAR, DANIEL; RODRIGUES, BRUNO LIMA; ARROYES, MONTSERRAT; FERRER-PICON, ELENA; MILANSKI, MARCIANE; VELLOSO, LICIO AUGUSTO; et al. Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn's disease. JOURNAL OF TRANSLATIONAL MEDICINE, v. 18, n. 1, . (16/01638-7)
COOPE, ANDRESSA; PASCOAL, LIVIA BITENCOURT; BOTEZELLI, JOSE DIEGO; RAMOS DA SILVA, FRANCESCA APARECIDA; SETSUKO AYRIZONO, MARIA DE LOURDES; RODRIGUES, BRUNO LIMA; MILANSKI, MARCIANE; CARVALHO, RITA BARBOSA; FAGUNDES, JOAO JOSE; VELLOSO, LICIO AUGUSTO; et al. ER stress activation in the intestinal mucosa but not in mesenteric adipose tissue is associated with inflammation in Crohn's disease patients. PLoS One, v. 14, n. 9, . (16/01638-7)

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