Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: UMLS:C0032463 (
polycythemia vera
)
3,374
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Activated erythropoietin (EPO) receptor (EPOR) signaling causes erythrocytosis. The important role of macrophages for the erythroid expansion and differentiation process has been reported, both in baseline and stress erythropoiesis. However, the significance of EPOR signaling for regulation of macrophages contributing to erythropoiesis has not been fully understood. Here we show that EPOR signaling activation quickly expands both erythrocytes and macrophages
in vivo
in mouse models of primary and secondary erythrocytosis. To mimic the chimeric condition and expansion of the disease clone in the
polycythemia vera
patients, we combined Cre-inducible
Jak2
V617F/+
allele with
LysM
-Cre allele which expresses in mature myeloid cells and some of the HSC/Ps (
LysM
-Cre;
Jak2
V617F/+
mice). We also generated inducible EPO-mediated secondary erythrocytosis models using
Alb
-Cre, Rosa26-loxP-stop-loxP
-rtTA, and doxycycline inducible
EPAS1
-double point mutant (DPM) alleles (
Alb
-Cre;DPM mice). Both models developed a similar degree of erythrocytosis. Macrophages were also increased in both models without increase of major inflammatory cytokines and chemokines. EPO administration also quickly induced these macrophages in wild-type mice before observable erythrocytosis. These findings suggest that EPOR signaling activation could induce not only erythroid cell expansion, but also macrophages. Surprisingly, an
in vivo
genetic approach indicated that most of those macrophages do not express EPOR, but erythroid cells and macrophages contacted tightly with each other. Given the importance of the central macrophages as a niche for erythropoiesis, further elucidation of the EPOR signaling mediated-regulatory mechanisms underlying macrophage induction might reveal a potential therapeutic target for erythrocytosis.
...
PMID:Expansion of EPOR-negative macrophages besides erythroblasts by elevated EPOR signaling in erythrocytosis mouse models. 2905 Dec 79
