Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently discovered peptide hormone hepcidin is the key regulator of systemic iron homeostasis. Iron metabolism is regulated in response to variations in hepcidin plasma levels. Hepcidin levels that are inappropriately low or high result in iron overload or iron deficiency, respectively. The early studies showed that hypoxia, iron concentration, and inflammation influence hepcidin levels, but the exact mechanism remained elusive. Very recently, different research groups discovered that IL-6, through the Jak/STAT-3 signaling pathway, is involved in regulation of hepcidin levels in response to inflammatory stimuli. In this review we present a general view of hepcidin biology, with emphasis on regulation in inflammatory conditions.
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PMID:IL-6 - STAT-3 - hepcidin: linking inflammation to the iron metabolism. 1833 66

Hepcidin is the master regulatory hormone of systemic iron metabolism. Hepcidin deficiency causes common iron overload syndromes whereas its overexpression is responsible for microcytic anemias. Hepcidin transcription is activated by the bone morphogenetic protein (BMP) and the inflammatory JAK-STAT pathways, whereas comparatively little is known about how hepcidin expression is inhibited. By using high-throughput siRNA screening we identified SMAD7 as a potent hepcidin suppressor. SMAD7 is an inhibitory SMAD protein that mediates a negative feedback loop to both transforming growth factor-beta and BMP signaling and that recently was shown to be coregulated with hepcidin via SMAD4 in response to altered iron availability in vivo. We show that SMAD7 is coregulated with hepcidin by BMPs in primary murine hepatocytes and that SMAD7 overexpression completely abolishes hepcidin activation by BMPs and transforming growth factor-beta. We identify a distinct SMAD regulatory motif (GTCAAGAC) within the hepcidin promoter involved in SMAD7-dependent hepcidin suppression, demonstrating that SMAD7 does not simply antagonize the previously reported hemojuvelin/BMP-responsive elements. This work identifies a potent inhibitory factor for hepcidin expression and uncovers a negative feedback pathway for hepcidin regulation, providing insight into a mechanism how hepcidin expression may be limited to avoid iron deficiency.
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PMID:SMAD7 controls iron metabolism as a potent inhibitor of hepcidin expression. 2004 Jul 61

Hepcidin, an antimicrobial peptide described as a key regulator of iron metabolism, is known to respond in mammals to several stimuli, including iron overload, anemia, hypoxia and inflammation, through a number of molecular pathways. In order to understand the molecular pathways involved in the regulation of hepcidin expression in teleost fish, we have isolated for European sea bass (Dicentrarchus labrax) several coding sequences of known molecules involved on these pathways in mammals, namely jak3, stat3, tmprss6, bmp6, bmpr2, hjv, smad4, smad5, tfr1 and tfr2. The transcription levels of the isolated genes were evaluated by real-time PCR on fish subjected to experimental iron modulation (overload/deficiency) or infection with Photobacterium damsela. Results show that genes associated with the major pathway of the inflammatory response (IL6/JAK/STAT pathway) in mammals are also modulated in sea bass, being up-regulated during infection. Similarly, genes of the pathways classically associated with the response to variations in iron status (the HJV/BMP/SMAD and HFE/TfR pathways) are also modulated, mostly through down-regulation in iron deficiency and up-regulation during iron overload. Interestingly, many of these genes are also found to be up-regulated during infection, which may indicate a crosstalk between the known pathways of hepcidin regulation. These observations suggest the evolutionary conservation of the mechanisms of hepcidin regulation in teleost fish.
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PMID:Molecular mechanisms of hepcidin regulation in sea bass (Dicentrarchus labrax). 2201 26

Anemia of chronic disease (ACD) or inflammation may be secondary to infections, autoimmune disorders, chronic renal failure, or malignancies. It is characterized by an immune activation with an increase in inflammatory cytokines and resultant increase in hepcidin levels. In addition, inappropriate erythropoietin levels or hyporesponsiveness to erythropoietin and reduced red blood cell survival contribute to the anemia. Hepcidin being the central regulator of iron metabolism plays a key role in the pathophysiology of ACD. Hepcidin binds to the iron export protein, ferroportin, present on macrophages, hepatocytes, and enterocytes, causing degradation of the latter. This leads to iron trapping within the macrophages and hepatocytes, resulting in functional iron deficiency. Production of hepcidin is in turn regulated by iron stores, inflammation, and erythropoiesis via the BMP-SMAD and JAK-STAT signaling pathways. Treatment of anemia should primarily be directed at the underlying disease, and conventional therapy such as red blood cell transfusions, iron, erythropoietin, and novel agents targeting the hepcidin-ferroportin axis and signaling pathways (BMP-SMAD, JAK-STAT) involved in hepcidin production also may be considered.
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PMID:Anemia of chronic disease. 2395 40