Changes in hepatic gene expression in dogs with experimentally induced nutritional iron deficiency

Fry, Michael M.; Kirk, Claudia A.; Liggett, Jason L.; Daniel, Gregory B.; Baek, Seung Joon; Gouffon, Julia S.; Chimakurthy, Pradeep M.; Rekapalli, Bhanu

doi:10.1111/j.1939-165x.2008.00081.x

Cited by 12 publications

(11 citation statements)

References 17 publications

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“…Iron deficiency was also considered to be the cause of decrease in hepatic non-heme iron content and hepcidin gene expression during the later period in this experiment. It has been reported that hepcidin gene expression markedly decreases in dogs with experimentally induced nutritional iron deficiency [14]. However, the hepatic non-heme iron content and hepcidin gene expression returned to the levels seen before turpentine injection, and the intensity of bone marrow iron staining did not decrease in the later period in this experiment.…”

Section: Discussionmentioning

confidence: 49%

Change in Serum Ferritin Concentration in Experimentally Induced Anemia of Chronic Inflammation in Dogs

et al. 2013

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In veterinary medicine, hyperferritinemia is often observed in dogs with various diseases (e.g., histiocytic sarcoma and immune-mediated hemolytic anemia) without evidence of iron overload. The mechanism underlying hyperferritinemia development is not well understood. Anemia caused by inflammation is termed as anemia of chronic disease (ACD), and experimentally induced ACD is known to cause slight hyperferritinemia. However, almost all these studies were based on short-term acute inflammation. Hepcidin, a protein mainly produced by hepatocytes, is thought to be a key regulator in iron release from reticuloendothelial cells (RECs), and its expression is related to ACD. We hypothesized that in the case of long-term ACD, iron deposition in RECs increases through hepcidin, causing a diachronic increase in serum ferritin levels. In the present study, we used a canine model with repeated subcutaneous administration of turpentine oil every 3 days over a period of 42 days (15 injections) and induced long-term inflammatory conditions; furthermore, we evaluated the change in serum ferritin concentration. Hypoproliferative anemia, bone marrow iron deposition and hypoferremia, which are characteristic of ACD, were observed on administering the turpentine injections. Hepatic iron content, hepatic hepcidin mRNA expression and serum ferritin concentration increased during the early period after turpentine injection, but returned to normal levels later. These results show that experimentally induced long-term ACD caused hypoproliferative anemia without sustained increase in hepcidin expression and did not cause systemic iron overload. Thus, chronic inflammation may not contribute greatly to increase in hyperferritinemia.

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Section: Discussionmentioning

confidence: 49%

Change in Serum Ferritin Concentration in Experimentally Induced Anemia of Chronic Inflammation in Dogs

et al. 2013

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“…IL-6 was induced within three hours after injection of mice with LPS, and urinary hepcidin peaked at six hours, followed by a significant decrease in serum iron [38]. There is also clear evidence that natural and induced iron deficiency in animals or humans strongly correlates with increased tissue TfR1 expression [39][40][41][42][43][44]. Finally, published data demonstrate that iron supplementation inhibits and iron chelation enhances MACV or JUNV GP-mediated entry in two cell lines [11].…”

Section: Iron Sequestration Tfr1 Expression and Arenaviral Hemorrhamentioning

confidence: 99%

Transferrin receptor 1 in the zoonosis and pathogenesis of New World hemorrhagic fever arenaviruses

Choe

Jemielity

Abraham

et al. 2011

Current Opinion in Microbiology

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At least five New World arenaviruses cause severe human hemorrhagic fevers. These viruses are transmitted to humans through contact with their respective South American rodent hosts. Each uses human transferrin receptor 1 (TfR1) as its obligate receptor. Accidental similarities between human TfR1 and TfR1 orthologs of arenviral host species enable zoonoses, whereas mice and rats are not infectable because they lack these TfR1 determinants of infection. All pathogenic New World arenaviruses bind to a common region of the apical domain of TfR1. The ability of a New World arenavirus to use human TfR1 is absolutely predictive of its ability to cause hemorrhagic fevers in humans. Non-pathogenic arenaviruses, closely related to hemorrhagic fever arenaviruses, cannot utilize human TfR1 but efficiently enter cells through TfR1 orthologs of their native rodent hosts. Mutagenesis studies suggest that minor changes in the entry glycoproteins of these non-pathogenic viruses may allow human transmission. TfR1 is upregulated as a result of iron sequestration during the acute phase response to infection, and the severity of disease may result from amplification of viral replication during this response.

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“…Hypoxia has multiple effects on the expression of a vast array of genes, but this has been almost entirely investigated in vitro [8] or in experimental animals [9]. Iron deficiency is a common nutritional disorder, and it enhances pathways that are associated with hypoxia as iron is required for optimal activity of prolyl hydroxylases (PHDs) that are principal negative regulators of hypoxia inducible factors (HIFs) [10; 11]; iron deficiency also has hypoxia-unrelated metabolism-regulating roles [12; 13; 14; 15; 16]. Investigating the relationship between gene expression and the nutritional environment is important for understanding the complications of genetic disorders and for the development of optimal personalized approaches to medical care [17].…”

Section: Introductionmentioning

confidence: 99%

Iron deficiency modifies gene expression variation induced by augmented hypoxia sensing

Zhang

Fan

et al. 2014

Blood Cells, Molecules, and Diseases

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In congenital Chuvash polycythemia (CP), VHLR200W homozygosity leads to elevated hypoxia inducible factor (HIF) levels at normoxia. CP is often treated by phlebotomy resulting in iron deficiency, permitting us to examine the separate and synergistic effects of iron deficiency and HIF signaling on gene expression. We compared peripheral blood mononuclear cell gene expression profiles of eight VHLR200W homozygotes with 17 wildtype individuals with normal iron status and found 812 up-regulated and 2120 down-regulated genes at false discovery rate 0.05. Among differential genes we identified three major gene regulation modules involving induction of innate immune responses, alteration of carbohydrate and lipid metabolism, and down-regulation of cell proliferation, stress-induced apoptosis and T-cell activation. These observations suggest molecular mechanisms for previous observations in CP of lower blood sugar without increased insulin and low oncogenic potential. Studies including 16 additional VHLR200W homozygotes with low ferritin indicated that iron deficiency enhanced the induction effect of VHLR200W for 50 genes including hemoglobin synthesis loci but suppressed the effect for 107 genes enriched for HIF-2 targets. This pattern is consistent with potentiation of HIF-1α protein stability by iron deficiency but a trend for down-regulation of HIF-2α translation by iron deficiency overriding an increase in HIF-2α protein stability.

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Changes in hepatic gene expression in dogs with experimentally induced nutritional iron deficiency

Cited by 12 publications

References 17 publications

Change in Serum Ferritin Concentration in Experimentally Induced Anemia of Chronic Inflammation in Dogs

Change in Serum Ferritin Concentration in Experimentally Induced Anemia of Chronic Inflammation in Dogs

Transferrin receptor 1 in the zoonosis and pathogenesis of New World hemorrhagic fever arenaviruses

Iron deficiency modifies gene expression variation induced by augmented hypoxia sensing

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