HO1 (haem oxygenase 1) and Fpn (ferroportin) are key proteins for iron recycling from senescent red blood cells and therefore play a major role in controlling the bioavailability of iron for erythropoiesis. Although important aspects of iron metabolism in HO1-deficient (Hmox1−/−) mice have already been revealed, little is known about the regulation of Fpn expression and its role in HO1 deficiency. In the present study, we characterize the cellular and systemic factors influencing Fpn expression in Hmox1−/− bone marrow-derived macrophages and in the liver and kidney of Hmox1−/− mice. In Hmox1−/− macrophages, Fpn protein was relatively highly expressed under high levels of hepcidin in culture medium. Similarly, despite high hepatic hepcidin expression, Fpn is still detected in Kupffer cells and is also markedly enhanced at the basolateral membrane of the renal tubules of Hmox1−/− mice. Through the activity of highly expressed Fpn, epithelial cells of the renal tubules probably take over the function of impaired system of tissue macrophages in recycling iron accumulated in the kidney. Moreover, although we have found increased expression of FLVCR (feline leukaemia virus subgroup C receptor), a haem exporter, in the kidneys of Hmox1−/− mice, haem level was increased in these organs. Furthermore, we show that iron/haem-mediated toxicity are responsible for renal injury documented in the kidneys of Hmox1−/− mice.

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