Studies of Slc30a10 deficiency in mice reveal that intestinal iron transporters Dmt1 and ferroportin transport manganese.

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Tác giả: Mariam Aghajan, Olga Antipova, Thomas B Bartnikas, Lauren Chiu, Grace S Chong, Shuling Guo, Brian P Jackson, Heather L Kowalski, Barry Lai, Courtney J Mercadante, Milankumar Prajapati, Tracy Punshon, Martina Ralle, Jared Z Zhang

Ngôn ngữ: eng

Ký hiệu phân loại: 333.822 Coal

Thông tin xuất bản: United States : Cellular and molecular gastroenterology and hepatology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 740690

BACKGROUND AND AIMS: SLC11A2 (DMT1) and SLC40A1 (ferroportin) are essential for dietary iron absorption, but their role in manganese transport is debated. SLC30A10 deficiency causes severe manganese excess due to loss of gastrointestinal manganese excretion. Patients are treated with chelators but also respond to oral iron, suggesting that iron can outcompete manganese for absorption in this disease. Here we determine if Dmt1 and ferroportin can transport manganese using Slc30a10-deficient mice as a model. METHODS: Manganese absorption and levels and other disease parameters were assessed in Slc30a10 RESULTS: Manganese absorption was increased in Slc30a10-deficient mice despite manganese excess. Intestinal Dmt1 and ferroportin deficiency attenuated manganese absorption and excess in Slc30a10-deficient mice. Intestinal Slc30a10 deficiency increased manganese absorption and levels in the hemochromatosis mouse model. CONCLUSIONS: Aberrant absorption contributes prominently to SLC30A10 deficiency, a disease previously attributed to impaired excretion, and is dependent upon intestinal Dmt1 and ferroportin and exacerbated by loss of intestinal Slc30a10. This work expands our understanding of overlaps between manganese and iron transport and the mechanisms by which the body regulates absorption of two nutrients that can share transport pathways. We propose that a reconsideration of the role of Dmt1 and ferroportin in manganese homeostasis is warranted.
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