ANP32E, a Protein Involved in Steroid-Refractoriness in Ulcerative Colitis, Identified by a Systems Biology Approach.

Autor: Lorén V; IBD Research Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.; Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain., Garcia-Jaraquemada A; IBD Research Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain., Naves JE; IBD Research Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain., Carmona X; IBD Research Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain., Mañosa M; IBD Research Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.; Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain.; Gastroenterology Department, Germans Trias i Pujol University Hospital, Badalona, Catalonia, Spain., Aransay AM; Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain.; Genome Analysis Platform, CIC bioGUNE, Derio, Bizkaia, Spain., Lavin JL; Genome Analysis Platform, CIC bioGUNE, Derio, Bizkaia, Spain., Sánchez I; Functional Biology and Experimental Therapeutics Laboratory, Functional and Translational Neurogenetics Unit, Department of Neurosciences, Germans Trias i Pujol Research Institute, Badalona, Catalonia, Spain., Cabré E; IBD Research Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.; Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain.; Gastroenterology Department, Germans Trias i Pujol University Hospital, Badalona, Catalonia, Spain., Manyé J; IBD Research Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.; Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain., Domènech E; IBD Research Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.; Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain.; Gastroenterology Department, Germans Trias i Pujol University Hospital, Badalona, Catalonia, Spain.
Jazyk: angličtina
Zdroj: Journal of Crohn's & colitis [J Crohns Colitis] 2019 Mar 26; Vol. 13 (3), pp. 351-361.
DOI: 10.1093/ecco-jcc/jjy171
Abstrakt: Background and Aims: Steroid-refractoriness is a common and unpredictable phenomenon in ulcerative colitis [UC], but there are no conclusive studies on the molecular functions involved. We aimed to assess the mechanism of action related to steroid failure by integrating transcriptomic data from UC patients, and updated molecular data on UC and glucocorticoids.
Methods: MicroRNA [miRNA] and mRNA expression were evaluated by sequencing and microarrays, respectively, from rectal biopsies of patients with moderately-to-severe active UC, obtained before and on the third day of steroid treatment. The differential results were integrated into the mathematical models generated by a systems biology approach.
Results: This computational approach identified 18 proteins that stand out either by being associated with the mechanism of action or by providing a means to classify the patients according to steroid response. Their biological functions have been linked to inflammation, glucocorticoid-induced transcription and angiogenesis. All the selected proteins except ANP32E [a chaperone which has been linked to the exchange of H2A.z histone and promotes glucocorticoid receptor-induced transcription] had previously been related to UC and/or glucocorticoid-induced biological actions. Western blot and immunofluorescence assays confirmed the implication of this chaperone in steroid failure in patients with active UC.
Conclusions: A systems biology approach allowed us to identify a comprehensive mechanism of action of steroid-refractoriness, highlighting the key role of steroid-induced transcription and the potential implication of ANP32E in this phenomenon.
(Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze: MEDLINE
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