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

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Item Type:Article
Title:Renal damage-induced hepcidin accumulation contributes to anemia in angiotensinogen-deficient mice
Creators Name:Rodrigues, A.F., Boreggio, L., Lahuta, T., Qadri, F., Alenina, N., Barros, C.C., Todiras, M. and Bader, M.
Abstract:Angiotensin II (Ang II) is the most active peptide hormone produced by the reninangiotensin 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 liver and spleen were also depleted in the RAS-deficient line. Hepatic hepcidin expression was reduced as well as the one of its major regulator, 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 RASdeficient mice is exacerbated by iron deficiency which is secondary to the renal damage-induced hepcidin accumulation in the circulation.
Keywords:Renin-Angiotensin System, Anemia, Chronic Kidney Disease, Animals, Mice
Source:Clinical Science
ISSN:0143-5221
Publisher:Portland Press
Date:27 January 2025
Additional Information:Copyright © 2025 The Author(s). This is an Accepted Manuscript; not the final Version of Record. Archiving permitted only in line with the archiving policy of Portland Press Limited.
Official Publication:https://doi.org/10.1042/cs20241789
PubMed:View item in PubMed

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