دورية أكاديمية
أعرض في EDS

Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn's disease.

التفاصيل البيبلوغرافية
العنوان: Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn's disease.
المؤلفون: Shumway AJ; Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA., Shanahan MT; Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA., Hollville E; Institute of Medical Sciences, University of Aberdeen Foresterhill, Aberdeen, Scotland, United Kingdom, Chen K; Center for Gastrointestinal Biology and Disease.; Department of Genetics., Beasley C; Center for Gastrointestinal Biology and Disease., Villanueva JW; Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA., Albert S; Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA., Lian G; Center for Gastrointestinal Biology and Disease., Cure MR; Center for Gastrointestinal Biology and Disease., Schaner M; Center for Gastrointestinal Biology and Disease., Zhu LC; Department of Pathology and Laboratory Medicine, and., Bantumilli S; Department of Pathology and Laboratory Medicine, and., Deshmukh M; Neuroscience Center., Furey TS; Center for Gastrointestinal Biology and Disease.; Department of Genetics.; Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Sheikh SZ; Center for Gastrointestinal Biology and Disease.; Department of Genetics., Sethupathy P; Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA.
المصدر: JCI insight [JCI Insight] 2024 Feb 22; Vol. 9 (4). Date of Electronic Publication: 2024 Feb 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-
مواضيع طبية MeSH: Crohn Disease*/pathology , MicroRNAs*/genetics , MicroRNAs*/metabolism, Adult ; Animals ; Mice ; Humans ; Child ; Phenotype ; Inflammation
مستخلص: Crohn's disease (CD) is a chronic inflammatory gut disorder. Molecular mechanisms underlying the clinical heterogeneity of CD remain poorly understood. MicroRNAs (miRNAs) are important regulators of gut physiology, and several have been implicated in the pathogenesis of adult CD. However, there is a dearth of large-scale miRNA studies for pediatric CD. We hypothesized that specific miRNAs uniquely mark pediatric CD. We performed small RNA-Seq of patient-matched colon and ileum biopsies from treatment-naive pediatric patients with CD (n = 169) and a control cohort (n = 108). Comprehensive miRNA analysis revealed 58 miRNAs altered in pediatric CD. Notably, multinomial logistic regression analysis revealed that index levels of ileal miR-29 are strongly predictive of severe inflammation and stricturing. Transcriptomic analyses of transgenic mice overexpressing miR-29 show a significant reduction of the tight junction protein gene Pmp22 and classic Paneth cell markers. The dramatic loss of Paneth cells was confirmed by histologic assays. Moreover, we found that pediatric patients with CD with elevated miR-29 exhibit significantly lower Paneth cell counts, increased inflammation scores, and reduced levels of PMP22. These findings strongly indicate that miR-29 upregulation is a distinguishing feature of pediatric CD, highly predictive of severe phenotypes, and associated with inflammation and Paneth cell loss.
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معلومات مُعتمدة: P01 DK094779 United States DK NIDDK NIH HHS; R01 DK136262 United States DK NIDDK NIH HHS; R21 HD104922 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: Gastroenterology; Genetics; Inflammatory bowel disease
المشرفين على المادة: 0 (MicroRNAs)
0 (MIRN29 microRNA, mouse)
SCR Disease Name: Pediatric Crohn's disease
تواريخ الأحداث: Date Created: 20240222 Date Completed: 20240223 Latest Revision: 20240613
رمز التحديث: 20240613
مُعرف محوري في PubMed: PMC10967384
DOI: 10.1172/jci.insight.168800
PMID: 38385744
قاعدة البيانات: MEDLINE
الوصف
تدمد:2379-3708
DOI:10.1172/jci.insight.168800