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Citations to this article

The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice
Mirco Castoldi, … , Matthias W. Hentze, Martina U. Muckenthaler
Mirco Castoldi, … , Matthias W. Hentze, Martina U. Muckenthaler
Published March 1, 2011
Citation Information: J Clin Invest. 2011;121(4):1386-1396. https://doi.org/10.1172/JCI44883.
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Research Article Hepatology Article has an altmetric score of 7

The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice

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Abstract

Systemic iron homeostasis is mainly controlled by the liver through synthesis of the peptide hormone hepcidin (encoded by Hamp), the key regulator of duodenal iron absorption and macrophage iron release. Here we show that the liver-specific microRNA miR-122 is important for regulating Hamp mRNA expression and tissue iron levels. Efficient and specific depletion of miR-122 by injection of a locked-nucleic-acid–modified (LNA-modified) anti-miR into WT mice caused systemic iron deficiency, characterized by reduced plasma and liver iron levels, mildly impaired hematopoiesis, and increased extramedullary erythropoiesis in the spleen. Moreover, miR-122 inhibition increased the amount of mRNA transcribed by genes that control systemic iron levels, such as hemochromatosis (Hfe), hemojuvelin (Hjv), bone morphogenetic protein receptor type 1A (Bmpr1a), and Hamp. Importantly, miR-122 directly targeted the 3′ untranslated region of 2 mRNAs that encode activators of hepcidin expression, Hfe and Hjv. These data help to explain the increased Hamp mRNA levels and subsequent iron deficiency in mice with reduced miR-122 levels and establish a direct mechanistic link between miR-122 and the regulation of systemic iron metabolism.

Authors

Mirco Castoldi, Maja Vujic Spasic, Sandro Altamura, Joacim Elmén, Morten Lindow, Judit Kiss, Jens Stolte, Richard Sparla, Lorenza A. D’Alessandro, Ursula Klingmüller, Robert E. Fleming, Thomas Longerich, Hermann J. Gröne, Vladimir Benes, Sakari Kauppinen, Matthias W. Hentze, Martina U. Muckenthaler

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2009 Total
Citations: 4 3 7 8 7 10 7 6 7 11 11 12 14 18 4 1 130
Citation information
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Citations to this article in year 2023 (7)

Title and authors Publication Year
Relationship between iron overload caused by abnormal hepcidin expression and liver disease: A review.
Zheng H, Yang F, Deng K, Wei J, Liu Z, Zheng YC, Xu H
Medicine 2023
Expression of genes related to iron homeostasis in breast cancer.
Mutlu T, Ozoran E, Trabulus DC, Talu CK, Erhan D, Mete M, Guven M
Molecular Biology Reports 2023
Serum miRNA profiles are altered in patients with primary sclerosing cholangitis receiving high-dose ursodeoxycholic acid
Hochberg JT, Sohal A, Handa P, Maliken BD, Kim TK, Wang K, Gochanour E, Li Y, Rose JB, Nelson JE, Lindor KD, LaRusso NF, Kowdley KV
2023
Differential Modulation of miR-122 Transcription by TGFβ1/BMP6: Implications for Nonresolving Inflammation and Hepatocarcinogenesis.
Paluschinski M, Kordes C, Vucur M, Buettner V, Roderburg C, Xu HC, Shinte PV, Lang PA, Luedde T, Castoldi M
Cells 2023
Uncovering Novel Roles of miR-122 in the Pathophysiology of the Liver: Potential Interaction with NRF1 and E2F4 Signaling
Paluschinski M, Schira-Heinen J, Pellegrino R, Heij LR, Bednarsch J, Neumann UP, Longerich T, Stuehler K, Luedde T, Castoldi M
Cancers 2023
Circulating microRNAs and hepcidin as predictors of iron homeostasis and anemia among school children: a biochemical and cross-sectional survey analysis.
Al-Rawaf HA, Gabr SA, Iqbal A, Alghadir AH
European Journal of Medical Research 2023
Nutritional Modulation of Hepcidin in the Treatment of Various Anemic States
D\u2019Andrea P, Giampieri F, Battino M
Nutrients 2023

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