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Divalent metal-ion transporter 1 is decreased in intestinal epithelial cells and contributes to the anemia in inflammatory bowel disease

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机构: [1]Department of Gastroenterology, The Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, China [2]Departments of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA [3]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
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Divalent metal-ion transporter 1 (DMT1) has been found to play an important role in the iron metabolism and hemogenesis. However, little is known about the potential role of DMT1 in the pathogenesis of anemia from patients with inflammatory bowel disease (IBD). Herein, we investigated expression of DMT1 in the intestinal mucosa by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry, and found that DMT1 was significantly decreased in the inflamed mucosa of active IBD patients compared with that in those patients at remission stage and healthy controls. To further study the mechanism, we cultured HCT 116 cell line in vitro. Expression of DMT1 in HCT116 was demonstrated to be markedly decreased under stimulation with TNF for 24 and 48 h, while JNK inhibitor (JNK-IN-7) could significantly reverse the decrease. Interestingly, anti-TNF therapy successfully improved anemia in clinical responsive Crohn's disease patients, and DMT1 was found to be markedly up-regulated in intestinal mucosa. Taken together, our studies demonstrate that decreased expression of DMT1 in intestinal mucosa leads to compromised absorption and transportation of iron and that blockade of TNF could rescue anemia and promote DMT1 expression in gut mucosa. This work provides a therapeutic approach in the management of anemia in IBD.

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出版当年[2016]版:
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
最新[2023]版:
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Department of Gastroenterology, The Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, China
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