Abnormal Small Intestinal Epithelial Microvilli in Patients With Crohn's Disease

Gastroenterology
Kelli L VanDussenThaddeus S Stappenbeck

Abstract

Crohn disease (CD) presents as chronic and often progressive intestinal inflammation, but the contributing pathogenic mechanisms are unclear. We aimed to identify alterations in intestinal cells that could contribute to the chronic and progressive course of CD. We took an unbiased system-wide approach by performing sequence analysis of RNA extracted from formalin-fixed paraffin-embedded ileal tissue sections from patients with CD (n = 36) and without CD (controls; n = 32). We selected relatively uninflamed samples, based on histology, before gene expression profiling; validation studies were performed using adjacent serial tissue sections. A separate set of samples (3 control and 4 CD samples) was analyzed by transmission electron microscopy. We developed methods to visualize an overlapping modular network of genes dysregulated in the CD samples. We validated our findings using biopsy samples (110 CD samples for gene expression analysis and 54 for histologic analysis) from the UNITI-2 phase 3 trial of ustekinumab for patients with CD and healthy individuals (26 samples used in gene expression analysis). We identified gene clusters that were altered in nearly all CD samples. One cluster encoded genes associated with the enterocy...Continue Reading

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Citations

Nov 8, 2018·Molecular Biology of the Cell·Julia A PinetteMatthew J Tyska
Mar 17, 2019·Journal of Crohn's & Colitis·Alka A PotdarJanine Bilsborough
Feb 28, 2020·Nature·Daniel B Graham, Ramnik J Xavier
Sep 26, 2019·Inflammatory Bowel Diseases·Mark T OstermanJulia J Liu
Sep 24, 2020·Inflammatory Bowel Diseases·Mark T OstermanJulia J Liu
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Jul 1, 2020·The Journal of Clinical Investigation·Katarzyna BulekXiaoxia Li
Mar 20, 2021·Frontiers in Cell and Developmental Biology·Xuebing HanGang Liu
Oct 1, 2021·The Tohoku Journal of Experimental Medicine·Yuji FujitaShigemi Yoshihara
Dec 21, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Emilie BersuderIsabelle Gross

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