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

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.

21364282

Projects: B1.3: Linking modulation of iron metabolism with the impact of macrophag...

J. Clin. Invest.
J. Clin. Invest. 121(4): 1386-96
3rd Mar 2011

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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[Lorenza D'Alessandro] [Ursula Klingmüller] [Matthias Hentze] [Martina Muckenthaler]

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Cell, Liver and Organism
Views: 2454
  • Created: 11th Jul 2012 at 10:47
  • Last updated: 24th Oct 2013 at 16:19

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