RESEARCH ARTICLE
High SMAD7 and p-SMAD2,3 expression is associated with Environmental Enteropathy in children Sana Syed1,2☯, Vincenzo Dinallo3☯, Najeeha T. Iqbal1, Laura Di Iorio3, Davide Di Fusco3, Shan Guleria2, Beatrice C. Amadi4, Kamran Sadiq1, Christopher Moskaluk1, S. Asad Ali1‡, Paul Kelly4,5‡, Giovanni Monteleone3‡*
a1111111111 a1111111111 a1111111111 a1111111111 a1111111111
1 Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan, 2 Department of Pediatrics, Division of Gastroenterology, Hepatology, & Nutrition, University of Virginia, Charlottesville, United States of America, 3 Department of Systems Medicine, University of Rome ’Tor Vergata’, Rome, Italy, 4 Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia, 5 Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom ☯ These authors contributed equally to this work. ‡ SAA, PK, and GM also contributed equally to this work. *
[email protected]
OPEN ACCESS Citation: Syed S, Dinallo V, Iqbal NT, Di Iorio L, Di Fusco D, Guleria S, et al. (2018) High SMAD7 and p-SMAD2,3 expression is associated with Environmental Enteropathy in children. PLoS Negl Trop Dis 12(2): e0006224. https://doi.org/10.1371/ journal.pntd.0006224 Editor: Joseph M. Vinetz, University of California San Diego School of Medicine, UNITED STATES Received: October 10, 2017 Accepted: January 9, 2018 Published: February 7, 2018 Copyright: © 2018 Syed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by grants from the Bill & Melinda Gates Foundation (SAA: OPP1066200, PK: OPP1066118, GM: OPP1131242). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: G. Monteleone has filed a patent related to the treatment of inflammatory
Abstract Enteropathies such as Crohn’s disease are associated with enteric inflammation characterized by impaired TGF-β signaling, decreased expression of phosphorylated (p)-SMAD2,3 and increased expression of SMAD7 (an inhibitor of SMAD3 phosphorylation). Environmental enteropathy (EE) is an acquired inflammatory disease of the small intestine (SI), which is associated with linear growth disruption, cognitive deficits, and reduced oral vaccine responsiveness in children
