Renal damage-induced hepcidin accumulation contributes to anemia in angiotensinogen-deficient mice.

IF 6.7 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
André F Rodrigues, Laura Boreggio, Tetiana Lahuta, Fatimunnisa Qadri, Natalia Alenina, Carlos C Barros, Mihail Todiras, Michael Bader
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引用次数: 0

Abstract

Angiotensin II (Ang II) is the most active peptide hormone produced by the renin-angiotensin system (RAS). Genetic deletion of genes that ultimately restrict Ang II formation has been shown to result in marked anemia in mice. In this study, adult mice with a genetic deletion of the RAS precursor protein angiotensinogen (Agt-KO) were used. Experimental analyses included capillary hematocrit, hemogram, plasma and tissue iron quantifications, expression analyses of genes encoding relevant proteins for body iron homeostasis in different organs, as well as plasma and urine hepcidin quantifications. As previously reported, Agt-KO were anemic with reduced red blood cell counts. Interestingly, we found that they presented microcytic anemia based on the reduced red blood cell volume. In agreement, plasma quantification of iron revealed lower levels of circulating iron in Agt-KO. The major body iron stores, namely in the liver and spleen, were also depleted in the RAS-deficient line. Hepatic hepcidin expression was reduced, as well as one of its major regulators, BMP6, as a result of the iron deficiency. However, plasma hepcidin levels were unexpectedly increased in Agt-KO. We confirm the typical morphological alterations and impaired renal function of Agt-KO and conclude that hepcidin accumulates in the circulation due to the reduced glomerular filtration in Agt-KO, and therefore identified the culprit of iron deficiency in Agt-KO. Collectively, the data demonstrated that the severe anemia developed in RAS-deficient mice is exacerbated by iron deficiency which is secondary to the renal damage-induced hepcidin accumulation in the circulation.

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来源期刊
Clinical science
Clinical science 医学-医学:研究与实验
CiteScore
11.40
自引率
0.00%
发文量
189
审稿时长
4-8 weeks
期刊介绍: Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health. Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively: Cardiovascular system Cerebrovascular system Gastrointestinal tract and liver Genomic medicine Infection and immunity Inflammation Oncology Metabolism Endocrinology and nutrition Nephrology Circulation Respiratory system Vascular biology Molecular pathology.
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