Gastrin-deficient mice have disturbed hematopoiesis in response to iron deficiency.
Gastrin-deficient mice have disturbed hematopoiesis in response to iron deficiency.
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DOI：
10.1210/en.2010-1474
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发表时间：
2011-06
期刊：
影响因子：
4.8
通讯作者：
S. Kovac;G. Anderson;W. Alexander;A. Shulkes;G. Baldwin
中科院分区：
文献类型：
--
作者：
S. Kovac;G. Anderson;W. Alexander;A. Shulkes;G. Baldwin
胃泌素是对胃酸分泌和胃肠粘膜生长很重要的肽激素。我们之前已经证明，三价铁离子与胃泌素结合，胃泌素-三价铁离子复合物在体外与铁转运蛋白转铁蛋白相互作用，并且循环胃泌素浓度与体内转铁蛋白饱和度呈正相关。在这里，我们报告了长期膳食铁调整对胃泌素缺乏（Gas（-/-））和高胃泌素缩胆素受体2缺陷（Cck2r（-/-））小鼠的影响，这两种小鼠的基础胃酸分泌均减少。除非动物受到缺铁的挑战，否则两种菌株的铁稳态似乎都正常。当喂食缺铁饮食时，Gas(-/-) 小鼠而非 Cck2r(-/-) 小鼠出现严重贫血。在缺铁的 Gas(-/-) 小鼠中，脾脏肿大也很明显，脾巨核细胞数量增加并伴有血小板增多。编码铁调节肽铁调素 Hamp 的 mRNA 表达在低铁饮食的 Cck2r(-/-) 和 Gas(-/-) 小鼠中均下调，但有趣的是，与相应的野生型小鼠相比，Cck2r(-/-) 小鼠的下调幅度更大，Gas(-/-) 小鼠的下调幅度更小。这些数据表明，胃泌素在缺铁条件下的造血过程中发挥着重要的直接作用，与其刺激酸分泌的能力无关。
Gastrins are peptide hormones important for gastric acid secretion and growth of the gastrointestinal mucosa. We have previously demonstrated that ferric ions bind to gastrins, that the gastrin-ferric ion complex interacts with the iron transport protein transferrin in vitro, and that circulating gastrin concentrations positively correlate with transferrin saturation in vivo. Here we report the effect of long-term dietary iron modification on gastrin-deficient (Gas(-/-)) and hypergastrinemic cholecystokinin receptor 2-deficient (Cck2r(-/-)) mice, both of which have reduced basal gastric acid secretion. Iron homeostasis in both strains appeared normal unless the animals were challenged by iron deficiency. When fed an iron-deficient diet, Gas(-/-) mice, but not Cck2r(-/-) mice, developed severe anemia. In iron-deficient Gas(-/-) mice, massive splenomegaly was also apparent with an increased number of splenic megakaryocytes accompanied by thrombocytosis. The expression of the mRNA encoding the iron-regulatory peptide hepcidin, Hamp, was down-regulated in both Cck2r(-/-) and Gas(-/-) mice on a low-iron diet, but, interestingly, the reduction was greater in Cck2r(-/-) mice and smaller in Gas(-/-) mice than in the corresponding wild-type strains. These data suggest that gastrins play an important direct role, unrelated to their ability to stimulate acid secretion, in hematopoiesis under conditions of iron deficiency.