کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3882945 1249357 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hepcidin regulates intrarenal iron handling at the distal nephron
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
Hepcidin regulates intrarenal iron handling at the distal nephron
چکیده انگلیسی

Hepcidin, the key regulatory hormone of iron homeostasis, and iron carriers such as transferrin receptor1 (TFR1), divalent metal transporter1 (DMT1), and ferroportin (FPN) are expressed in kidney. Whether hepcidin plays an intrinsic role in the regulation of renal iron transport is unknown. Here, we analyzed the renal handling of iron in hemochromatosis Hepc -/- and Hjv -/- mouse models, as well as in phenylhydrazine (PHZ)-treated mice. We found a marked medullary iron deposition in the kidneys of Hepc -/- mice, and iron leak in the urine. The kidneys of Hepc -/- mice exhibited a concomitant decrease in TFR1 and increase in ferritin and FPN expression. Increased FPN abundance was restricted to the thick ascending limb (TAL). DMT1 protein remained unaffected despite a significant decrease of its mRNA level, suggesting that DMT1 protein is stabilized in the absence of hepcidin. Treatment of kidney sections from Hepc -/- mice with hepcidin decreased DMT1 protein, an effect confirmed in renal cell lines where hepcidin markedly decreased 55Fe transport. In the kidneys of Hjv -/- mice exhibiting low hepcidin expression, the iron overload was similar to that in the kidneys of Hepc -/- mice. However, in PHZ mice, iron accumulation resulting from hemoglobin leak was detected in the proximal tubule. Thus, kidneys exhibit a tissue-specific handling of iron that depends on the extra iron source. Hepcidin may control the expression of iron transporters to prevent renal iron overload.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 84, Issue 4, October 2013, Pages 756–766
نویسندگان
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