Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis.

Eckard, Jonathan; Dai, Jisen; Wu, Jing; Jian, Jinlong; Yang, Qing; Chen, Haobin; Costa, Max; Frenkel, Krystyna; Huang, Xi

doi:10.1186/1475-2867-10-28

Cited by 43 publications

(37 citation statements)

References 47 publications

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“…The down-regulation of myelination-related genes and up-regulation of those related to angiogenesis is in line with previous reports that ID leads to hypo-myelination and increased angiogenesis (Beard et al, 2003; Todorich et al, 2009; Eckard et al, 2010). Hypo-myelination is also characteristic of RLS in humans (Connor et al, 2011).…”

Section: Discussionsupporting

confidence: 92%

Iron deficiency alters expression of dopamine-related genes in the ventral midbrain in mice

Jellen

Wang

et al. 2013

Neuroscience

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A clear link exists between iron deficiency (ID) and nigrostriatal dopamine malfunction. This link appears to play an important role in at least restless legs syndrome (RLS) if not several other neurological diseases. Yet, the underlying mechanisms remain unclear. The effects of ID on gene expression in the brain have not been studied extensively. Here, to better understand how exactly ID alters dopamine functioning, we investigated the effects of ID on gene expression in the brain, seeking to identify any potential transcription-based mechanisms. We used six strains of recombinant inbred mice (BXD type) known to differ in susceptibility to ID in the brain. Upon weaning, we subjected mice from each strain to either an iron-deficient or iron-adequate diet. After 100 days of dietary treatment, we measured the effects of ID on gene expression in the ventral midbrain (VMB), a region containing the substantia nigra. The substantia nigra is the base of the nigrostriatal dopamine pathway and a region particularly affected by iron loss in RLS. We screened for ID-induced changes in expression, including changes in that of both iron-regulating and dopamine-related genes. Results revealed a number of expression changes occurring in ID, with large strain-based differences in the genes involved and number of expression changes occurring. In terms of dopamine-related genes, results revealed ID-induced expression changes in three genes with direct ties to nigrostriatal dopamine functioning, two of which have never before been implicated in an iron-dopamine pathway. These were stromal cell-derived factor 1 (Cxcl12, or SDF-1), a ferritin regulator and potent dopamine neuromodulator, and hemoglobin, beta adult chain 1 (Hbb-b1), a gene recently shown to play a functional role in dopaminergic neurons. The extent of up-regulation of these genes varied by strain. This work not only demonstrates wide genetic variation in the transcriptional response to ID in the brain, but also reveals two novel biochemical pathways by which iron may potentially alter dopamine function.

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Section: Discussionsupporting

confidence: 92%

Iron deficiency alters expression of dopamine-related genes in the ventral midbrain in mice

Jellen

Wang

et al. 2013

Neuroscience

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“…However, TfR1 expression is also regulated at the transcriptional level. TfR1 expression is up-regulated by the hypoxia-inducible factor (6), which is typically activated under hypoxic conditions (7), but can also be turned on by a number of non-hypoxic stimuli, including inflammatory signals such as nitric oxide and l/opolysaccharide in macrophages (8) and 17␤-estradiol in estrogen receptor-positive cells (9).…”

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confidence: 99%

Src Regulates Tyr20 Phosphorylation of Transferrin Receptor-1 and Potentiates Breast Cancer Cell Survival

Jian

Yang

Huang

2011

Journal of Biological Chemistry

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Background:The role of transferrin receptor-1 (TfR1) in cell signaling remains unknown. Results: Using gambogic acid, we found that TfR1 is bound to Src and its phosphorylation at Tyr 20 potentiates breast cancer cell survival. Conclusion: In addition to its iron uptake function, TfR1 is involved in cell survival. Significance: High expression of TfR1 in cancer cells presents a therapeutic target for gambogic acid and Src inhibitor.

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“…This limitation might affect the specificity of proposed criteria and a validation study will be required. We also have to raise false-positive conditions potentially associated with elevated serum VEGF, including iron deficiency,23 anaemia,24 hypoxia25 and various types of cancer 25. Patients with breast, gastrointestinal or prostate cancer present further increase in VEGF levels on metastatic stage 25.…”

Section: Discussionmentioning

confidence: 99%

Proposal of new clinical diagnostic criteria for POEMS syndrome

Suichi

Misawa

Sato

et al. 2018

J Neurol Neurosurg Psychiatry

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ObjectiveTo propose the optimal diagnostic criteria for polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome using appropriate statistical methods and disease controls.MethodsThis retrospective cohort study included 104 consecutive patients with suspected POEMS syndrome, among whom a gold standard group of 60 patients with definitive POEMS syndrome diagnosis were followed for at least 12 months to strictly exclude other disorders mimicking POEMS syndrome and to confirm response to POEMS syndrome-specific treatment. Thirty patients with chronic inflammatory demyelinating polyradiculoneuropathy (demyelinating polyradiculoneuropathy controls) and 30 with multiple myeloma or immunoglobulin light chain amyloidosis (monoclonal plasma cell proliferation controls) were also included. Logistic regression analyses were performed to determine optimal combination of clinical and laboratory abnormalities, characteristic of POEMS syndrome.ResultsThe diagnostic criteria were statistically defined as the presence of the three major criteria (polyneuropathy (typically demyelinating), monoclonal plasma cell proliferative disorder and elevated vascular endothelial growth factor) and at least two of the four minor criteria (oedema/effusion, skin changes, organomegaly and sclerotic bone lesions), based on best performance by area under the receiver operating characteristic curve analyses. The sensitivity and specificity were 100% and 100%, respectively; the diagnostic accuracy of the proposed criteria was equivalent to somewhat complicated previous criteria.ConclusionsThe statistically defined, simple diagnostic criteria for POEMS syndrome could accelerate early diagnosis and treatment, thereby contribute to better outcome in patients with this serious disease. Prospective larger studies are required to confirm the validity.

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Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis.

Cited by 43 publications

References 47 publications

Iron deficiency alters expression of dopamine-related genes in the ventral midbrain in mice

Iron deficiency alters expression of dopamine-related genes in the ventral midbrain in mice

Src Regulates Tyr20 Phosphorylation of Transferrin Receptor-1 and Potentiates Breast Cancer Cell Survival

Proposal of new clinical diagnostic criteria for POEMS syndrome

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