A genetic mouse model of severe iron deficiency anemia reveals tissue-specific transcriptional stress responses and cardiac remodeling

Schwartz, Andrew J.; Converso‐Baran, Kimber; Michele, Daniel E.; Shah, Yatrik M.

doi:10.1074/jbc.ra119.009578

Cited by 20 publications

(14 citation statements)

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“…Decreased RBC and hemoglobin content during iron deficiency anemia leads to systemic tissue hypoxia [ 58 ]. The HIF transcription factors are central mediators of cellular adaptation to low oxygen (O 2 ) tension.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Down-Regulation of Copper-Related Genes and Decreased Ferroportin Protein Level in the Duodenum of Iron-Deficient Piglets

et al. 2020

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In mammals, 2 × 1012 red blood cells (RBCs) are produced every day in the bone marrow to ensure a constant supply of iron to maintain effective erythropoiesis. Impaired iron absorption in the duodenum and inefficient iron reutilization from senescent RBCs by macrophages contribute to the development of anemia. Ferroportin (Fpn), the only known cellular iron exporter, as well as hephaestin (Heph) and ceruloplasmin, two copper-dependent ferroxidases involved in the above-mentioned processes, are key elements of the interaction between copper and iron metabolisms. Crosslinks between these metals have been known for many years, but metabolic effects of one on the other have not been elucidated to date. Neonatal iron deficiency anemia in piglets provides an interesting model for studying this interplay. In duodenal enterocytes of young anemic piglets, we identified iron deposits and demonstrated increased expression of ferritin with a concomitant decline in both Fpn and Heph expression. We postulated that the underlying mechanism involves changes in copper distribution within enterocytes as a result of decreased expression of the copper transporter—Atp7b. Obtained results strongly suggest that regulation of iron absorption within enterocytes is based on the interaction between proteins of copper and iron metabolisms and outcompetes systemic regulation.

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Section: Discussionmentioning

confidence: 99%

Relationship between Down-Regulation of Copper-Related Genes and Decreased Ferroportin Protein Level in the Duodenum of Iron-Deficient Piglets

et al. 2020

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“…In agreement, the severity of patients' fibrosis inversely correlated with hepcidin levels. These observations may suggest that like in rats, 49 prolonged iron deficiency that represses hepcidin may likely increase the risk of fibrosis.…”

Section: How Alterations Of Intracellular Iron Levels Are Exploitedmentioning

confidence: 92%

“…47 Of medical interest, blocking of this interaction prevented P. vivax invasion in clinical isolates. Altogether, TFR1 is as a multifaceted receptor, and much remains to be learned about its distinct roles, both in iron acquisition for specialized cell functions as well as in mediating iron-independent signaling events critical for particular 49 The study revealed that the liver, spleen, and kidney, but not the heart, displayed transcriptional programs characteristic of hypoxia and cellular iron deficiency. Despite the lack of such stress responses, the heart showed profound tissue remodeling, hallmarked by cardiomegaly, and perturbation of cardiac function ( Figure 4A).…”

Section: Cellular Iron Acquisition Utilization and Storagementioning

confidence: 99%

“…This stays in agreement with previously mentioned liver damage in response to prolonged systemic iron deficiency. 49 Finally, combined IRPs depletion in macrophages renders mice more susceptible to the infection with the intracellular pathogen Salmonella typhimurium, likely in part mediated by the increased ferritin iron pool accessible to the bacteria (Figure 3). 97 This partially contrasts findings from macrophage-specific Fth KO animals that lack ferritin H, which rapidly succumb to intracellular Mycobacterium tuberculosis infection.…”

Section: Cellular Iron Handing By Ire/irp Regulatory Mechanisms -Cementioning

confidence: 99%

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Cell‐type‐specific insights into iron regulatory processes

Mleczko-Sanecka

Silvestri

2020

American J Hematol

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Despite its essential role in many biological processes, iron is toxic when in excess due to its propensity to generate reactive oxygen species. To prevent diseases associated with iron deficiency or iron loading, iron homeostasis must be tightly controlled. Intracellular iron content is regulated by the Iron Regulatory Element‐Iron Regulatory Protein (IRE‐IRP) system, whereas systemic iron availability is adjusted to body iron needs chiefly by the hepcidin‐ferroportin (FPN) axis. Here, we aimed to review advances in the field that shed light on cell‐type‐specific regulatory mechanisms that control or modify systemic and local iron balance, and how shifts in cellular iron levels may affect specialized cell functions.

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“…The elasticities of the aorta and left carotid were measured by using a combination of EKV-mode ultrasonography system with an MS250 transducer for arterial wall thickness (Vevo 2100, Fujifilm VisualSonics, Inc.) and carotid BP measured from the radio-telemetry system. Rats were anesthetized as previously described (60). Two-dimensional arterial ultrasound images of aorta and carotid were obtained near the aorta arch and left carotid sinus area in the supine position.…”

Section: Methodsmentioning

confidence: 99%

Potential role of intermittent functioning of baroreflexes in the etiology of hypertension in spontaneously hypertensive rats

Randall

Whitesall

et al. 2020

JCI Insight

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A genetic mouse model of severe iron deficiency anemia reveals tissue-specific transcriptional stress responses and cardiac remodeling

Cited by 20 publications

References 36 publications

Relationship between Down-Regulation of Copper-Related Genes and Decreased Ferroportin Protein Level in the Duodenum of Iron-Deficient Piglets

Relationship between Down-Regulation of Copper-Related Genes and Decreased Ferroportin Protein Level in the Duodenum of Iron-Deficient Piglets

Cell‐type‐specific insights into iron regulatory processes

Potential role of intermittent functioning of baroreflexes in the etiology of hypertension in spontaneously hypertensive rats

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