| Title | Endoplasmic reticulum stress and unfolded protein response are involved in paediatric inflammatory bowel disease |
|---|---|
| Publication Type | Articolo su Rivista peer-reviewed |
| Year of Publication | 2014 |
| Authors | Negroni, Anna, Prete E., Vitali Roberta, Cesi Vincenzo, Aloi M., Civitelli F., Cucchiara S., and Stronati L. |
| Journal | Digestive and Liver Disease |
| Volume | 46 |
| Pagination | 788-794 |
| ISSN | 15908658 |
| Keywords | activating transcription factor 4, activating transcription factor 6, adalimumab, adolescent, article, azathioprine, biological therapy, Child, childhood disease, clinical article, clinical trial, colon, colon biopsy, colon mucosa, colonoscope, colonoscopy, controlled study, corticosteroid, Crohn disease, Crohn Disease Activity Index, disease duration, DNA microarray, drug megadose, endoplasmic reticulum stress, Female, follow up, Follow-Up Studies, Gene expression, genetic analyzer, heat shock protein, heat shock protein 5, human, human tissue, Humans, Immunoblotting, Immunomodulation, inflammatory bowel disease, Inflammatory Bowel Diseases, infliximab, initiation factor 2alpha, inositol, inositol requiring enzyme 1, interleukin 8, Intestinal Mucosa, intestine biopsy, intestine mucosa, iron responsive element, low drug dose, major clinical study, male, mesalazine, messenger RNA, metabolism, methotrexate, midazolam, Middle Aged, multicenter study, pancreatic endoplasmic reticulum kinase, Pathology, Pediatric Crohn Disease Activity Index, pethidine, phosphotransferase, physiology, priority journal, procedures, Prospective Studies, prospective study, Protein, protein disulfide isomerase, protein disulfide isomerase family A member 4, protein expression, protein hspa5, protein p50, protein p90, protein pdia4, protein perk, protein phosphorylation, randomized controlled trial, real time polymerase chain reaction, RNA splicing, school child, signal transduction, ulcerative colitis, unclassified drug, unfolded protein response, upregulation, Western blotting, X box binding protein 1 |
| Abstract | Background: Endoplasmic reticulum stress and unfolded protein response have been recently associated with the development of inflammatory bowel diseases in adults. We aimed at assessing the involvement of these pathways also in paediatric inflammatory bowel disease by analysing the expression of the main genes involved in endoplasmic reticulum stress and correlating them with the degree of intestinal inflammation. Methods: Real-time PCR and Western blot analysis of the expression of the endoplasmic reticulum stress marker HSPA5 and of selected genes representing the three pathways of unfolded protein response (IRE-XBP1, PERK-ATF4, ATF6p90-p50) in inflamed and uninflamed biopsies from 28 inflammatory bowel disease paediatric patients and 10 controls. Results: HSPA5, PDIA4, as well as unspliced and spliced XBP1 mRNAs were significantly increased in patients' inflamed colonic mucosa compared to uninflamed mucosa and controls. HSPA5, PDIA4, ATF6, and phospho-IRE proteins were also upregulated, indicating the activation of the IRE-XBP1 and ATF6p90-p50 branches of unfolded protein response. A positive significant correlation between interleukin-8 levels, as a marker of inflammation, and upregulated genes was found in the inflamed colonic mucosa. Conclusion: A deregulation of the genes involved in the endoplasmic reticulum stress and unfolded protein response pathways may be a key component of the inflammatory response in paediatric patients with inflammatory bowel disease. © 2014 Editrice Gastroenterologica Italiana S.r.l. |
| Notes | cited By 2 |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84906302978&doi=10.1016%2fj.dld.2014.05.013&partnerID=40&md5=df9e12934de4ca9e1ffe466d7d72d65a |
| DOI | 10.1016/j.dld.2014.05.013 |
| Citation Key | Negroni2014788 |
