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

Wei Wu, Yang Song, Chong He, Changqin Liu, Ruijin Wu, Leilei Fang, Yingzi Cong, Yinglei Miao, Zhanju Liu

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Abstract

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.

Original languageEnglish (US)
Article number16344
JournalScientific Reports
Volume5
DOIs
StatePublished - Nov 17 2015

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Inflammatory Bowel Diseases
Anemia
Epithelial Cells
Ions
Intestinal Mucosa
Mucous Membrane
Iron
HCT116 Cells
solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
Crohn Disease
Real-Time Polymerase Chain Reaction
Cultured Cells
Immunohistochemistry
Cell Line
Therapeutics

ASJC Scopus subject areas

  • General

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Divalent metal-ion transporter 1 is decreased in intestinal epithelial cells and contributes to the anemia in inflammatory bowel disease. / Wu, Wei; Song, Yang; He, Chong; Liu, Changqin; Wu, Ruijin; Fang, Leilei; Cong, Yingzi; Miao, Yinglei; Liu, Zhanju.

In: Scientific Reports, Vol. 5, 16344, 17.11.2015.

Research output: Contribution to journalArticle

Wu, Wei ; Song, Yang ; He, Chong ; Liu, Changqin ; Wu, Ruijin ; Fang, Leilei ; Cong, Yingzi ; Miao, Yinglei ; Liu, Zhanju. / Divalent metal-ion transporter 1 is decreased in intestinal epithelial cells and contributes to the anemia in inflammatory bowel disease. In: Scientific Reports. 2015 ; Vol. 5.
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