ER stress activation in the intestinal mucosa but not in mesenteric adipose tissue is associated with inflammation in Crohn’s disease patients

Autoři: Andressa Coope aff001;  Lívia Bitencourt Pascoal aff001;  José Diego Botezelli aff001;  Francesca Aparecida Ramos da Silva aff001;  Maria de Lourdes Setsuko Ayrizono aff001;  Bruno Lima Rodrigues aff001;  Marciane Milanski aff002;  Rita Barbosa Carvalho aff003;  João José Fagundes aff001;  Lício Augusto Velloso aff004;  Raquel Franco Leal aff001
Působiště autorů: IBD Research Laboratory, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil aff001;  Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil aff002;  Department of Pathology, Gastrocenter, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil aff003;  Laboratory of Cell Signaling, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223105


Chronic/abnormal activation of endoplasmic reticulum (ER) stress is linked to the exacerbation of the inflammatory process and has been recently linked to Crohn’s disease (CD) pathophysiology. We investigated the intestinal mucosa and the mesenteric adipose tissue (MAT) collected from CD patients with active disease (CD group) and from non-IBD patients (CTR group) to study ER stress activation and to address tissue-specific modulation in CD. The intestinal mucosa of CD patients showed an upregulation in the expression of ER stress related genes, including ATF3, DNAJC3, STC2, DDIT3, CALR, HSPA5 and HSP90B1. Results showed that EIF2AK3 gene was upregulated, along with increased protein expression of p-eIF2α and p-eIF2α/eIF2α ratio. Additionally, ERN1 gene expression was upregulated, along with an increased spliced/activated form sXBP1 protein. Despite the upregulation of ATF6 gene expression in the intestinal mucosa of CD patients, no differences were found in ATF6 protein expression. Lastly, the analysis of MAT revealed unchanged levels of ER stress markers along with no differences in the activation of UPR. However, chaperone gene expression was modulated in the MAT of CD patients. To conclude, our results address tissue-specific differences in UPR activation in CD and point the ER stress as an important pro-inflammatory mechanism in CD, specifically in the intestinal mucosa.

Klíčová slova:

Adipose tissue – Crohn's disease – DNA transcription – Gastrointestinal tract – Gene expression – Inflammation – Inflammatory bowel disease – Surgical and invasive medical procedures


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