SLC39A14是遗传性血色素沉着症小鼠模型中肝细胞铁过载发展所必需的。
SLC39A14 Is Required for the Development of Hepatocellular Iron Overload in Murine Models of Hereditary Hemochromatosis.
作者信息
Jenkitkasemwong Supak, Wang Chia-Yu, Coffey Richard, Zhang Wei, Chan Alan, Biel Thomas, Kim Jae-Sung, Hojyo Shintaro, Fukada Toshiyuki, Knutson Mitchell D
机构信息
Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.
Department of Surgery, University of Florida, Gainesville, FL 32611, USA.
出版信息
Cell Metab. 2015 Jul 7;22(1):138-50. doi: 10.1016/j.cmet.2015.05.002. Epub 2015 May 28.
Nearly all forms of hereditary hemochromatosis are characterized by pathological iron accumulation in the liver, pancreas, and heart. These tissues preferentially load iron because they take up non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. Yet, how tissues take up NTBI is largely unknown. We report that ablation of Slc39a14, the gene coding for solute carrier SLC39A14 (also called ZIP14), in mice markedly reduced the uptake of plasma NTBI by the liver and pancreas. To test the role of SLC39A14 in tissue iron loading, we crossed Slc39a14(-/-) mice with Hfe(-/-) and Hfe2(-/-) mice, animal models of type 1 and type 2 (juvenile) hemochromatosis, respectively. Slc39a14 deficiency in hemochromatotic mice greatly diminished iron loading of the liver and prevented iron deposition in hepatocytes and pancreatic acinar cells. The data suggest that inhibition of SLC39A14 may mitigate hepatic and pancreatic iron loading and associated pathologies in iron overload disorders.
几乎所有形式的遗传性血色素沉着症都以肝脏、胰腺和心脏中的病理性铁蓄积为特征。这些组织优先摄取铁，因为它们会摄取非转铁蛋白结合铁（NTBI），铁过载时NTBI会出现在血浆中。然而，组织如何摄取NTBI在很大程度上尚不清楚。我们报告称，在小鼠中敲除编码溶质载体SLC39A14（也称为ZIP14）的基因Slc39a14，可显著降低肝脏和胰腺对血浆NTBI的摄取。为了测试SLC39A14在组织铁负荷中的作用，我们将Slc39a14(-/-)小鼠与分别作为1型和2型（青少年型）血色素沉着症动物模型的Hfe(-/-)和Hfe2(-/-)小鼠进行杂交。血色素沉着症小鼠中Slc39a14的缺乏极大地减少了肝脏的铁负荷，并防止了肝细胞和胰腺腺泡细胞中的铁沉积。数据表明，抑制SLC39A14可能减轻铁过载疾病中的肝脏和胰腺铁负荷以及相关病理状况。
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