title: Divalent metal-ion transporter 1 is decreased in intestinal epithelial cells and contributes to the anemia in inflammatory bowel disease.
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.
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Chong
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Changqin
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Ruijin
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Departments of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
authors.forename: Yinglei
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007501:Iron / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D055815:Young Adult; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D000911:Antibodies, Monoclonal; D027682:Cation Transport Proteins; D006454:Hemoglobins; D007501:Iron; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2