caa a22 4500 44579609X CHVBK 20180317145125.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s10620-010-1374-3 doi (NATIONALLICENCE)springer-10.1007/s10620-010-1374-3 Riboflavin Depletion Impairs Cell Proliferation in Adult Human Duodenum: Identification of Potential Effectors [Elektronische Daten] [Emi Nakano, Sohail Mushtaq, Paul Heath, Eun-Sook Lee, Jonathan Bury, Stuart Riley, Hilary Powers, Bernard Corfe] Background and Aims: Riboflavin (vitaminB2) is an essential dietary component with a known function in oxidative metabolism. Our previous data using a rat model of riboflavin deficiency suggested that riboflavin also functions as a luminal signaling molecule regulating crypt development and cell turnover. Riboflavin deficiency is prevalent in both high- and low-income countries across the globe. This study aims to establish whether riboflavin deficiency has consequences for gastrointestinal (GI) morphology in adults and what the effects and effectors of any such alteration may be. Methods: Duodenal biopsies and blood samples were collected from a cross-section of gastroscopy patients. Crypt morphology and cell division were studied by immunohistochemistry, and biochemical riboflavin status was determined. Additionally a cell culture model of riboflavin deficiency was developed and analyzed using a combination of flow cytometry, and microarray and clonogenic assays. Result: Duodenal crypts from subjects in the lowest quartile of riboflavin status were significantly shorter (P=0.023), less cellular (P=0.007), and had fewer cell divisions (P=0.034) than the crypts of subjects in the top quartile of riboflavin status. Following riboflavin depletion of colon cells in culture, cell cycle slowed. Microscopy revealed impaired mitosis and accumulation of aneuploid cells. Alterations in gene expression profiles reflected this alteration, with several mitosis-related genes altered, including AspM, cyclinB1, and Birc5 downregulated and Kif23 upregulated. Riboflavin depletion invitro caused irreversible loss of proliferative potential of cells. Conclusions: Riboflavin depletion in adult humans impairs proliferation and proliferative potential of intestinal cells, which may have implications for gastrointestinal function. Springer Science+Business Media, LLC, 2010 Riboflavin nationallicence Intestine nationallicence Proliferation nationallicence Mitosis nationallicence Nakano Emi Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut Mushtaq Sohail Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut Heath Paul Academic Neurology Unit, Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut Lee Eun-Sook Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut Bury Jonathan Academic Unit of Pathology; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut Riley Stuart Department of Gastroenterology, Northern General Hospital, Sheffield, UK aut Powers Hilary Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut Corfe Bernard Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/4(2011-04-01), 1007-1019 0163-2116 56:4<1007 2011 56 10620 https://doi.org/10.1007/s10620-010-1374-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1374-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nakano Emi Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut NATIONALLICENCE 700 1- Mushtaq Sohail Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut NATIONALLICENCE 700 1- Heath Paul Academic Neurology Unit, Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut NATIONALLICENCE 700 1- Lee Eun-Sook Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut NATIONALLICENCE 700 1- Bury Jonathan Academic Unit of Pathology; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut NATIONALLICENCE 700 1- Riley Stuart Department of Gastroenterology, Northern General Hospital, Sheffield, UK aut NATIONALLICENCE 700 1- Powers Hilary Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut NATIONALLICENCE 700 1- Corfe Bernard Human Nutrition Unit; Faculty of Medicine, Dentistry and Health, The University of Sheffield, Beech Hill Road, S10 2RX, Sheffield, UK aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/4(2011-04-01), 1007-1019 0163-2116 56:4<1007 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer