Intestinal iron absorption is appropriately modulated to match physiological demand for iron in wild-type and iron-loaded Hamp (hepcidin) knockout rats during acute colitis.
Intestinal iron absorption is appropriately modulated to match physiological demand for iron in wild-type and iron-loaded Hamp (hepcidin) knockout rats during acute colitis.
复制标题
DOI：
10.1371/journal.pone.0252998
复制
发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Collins JF
中科院分区：
文献类型：
--
作者：
Flores SRL;Nelson S;Woloshun RR;Wang X;Ha JH;Lee JK;Yu Y;Merlin D;Collins JF
黏膜损伤、屏障破坏、炎症和缺铁性贫血(IDA)是人类溃疡性结肠炎(UC)的典型特征。UC的贫血似乎主要与全身炎症有关。这种‘炎症性贫血’(AI)的发病机制涉及细胞因子介导的肝脏HAMP(编码铁调节激素，海普西丁)的反式激活。在人工智能中，高水平的海普西丁抑制了铁的吸收(和从储存中释放铁)，从而降低了血清铁，并限制了红细胞生成的铁(导致贫血)。在不太严重的疾病状态下，炎症可能仅限于肠道，但这是否会扰乱铁平衡还不确定。我们假设局部肠炎将增加总体铁需求(以支持免疫反应和组织修复)，而肝脏HAMP表达将减少，从而降低(即，增强)铁吸收。因此，我们建立了一种轻度急性结肠炎的大鼠模型，并研究了铁的吸收和体内平衡。口服DSS(4%)7天的大鼠出现肠道(但不是全身性)炎症，生物标记物分析表明铁的利用率提高。DSS处理的WT大鼠的铁吸收增加(2-3倍)，但出乎意料的是，肝脏HAMP的表达并未受到抑制。因此，为了更好地了解急性结肠炎时铁吸收的调节，我们使用了Hamp KO大鼠进行进一步的实验。HAMP KOS组DSS-结肠炎的严重程度与WT对照组相似。在KO中，与结肠炎的生理反应相关的铁需求的增加是通过动员肝脏储存的铁来满足的，而不是像WT大鼠那样通过增加肠内铁的吸收来满足。综上所述，无论性别还是基因类型的大鼠，铁的吸收都得到了适当的调节，以匹配急性肠道炎症期间对膳食铁的生理需求，但调节机制可能不涉及海普西丁。
Mucosal damage, barrier breach, inflammation, and iron-deficiency anemia (IDA) typify ulcerative colitis (UC) in humans. The anemia in UC appears to mainly relate to systemic inflammation. The pathogenesis of this ‘anemia of inflammation’ (AI) involves cytokine-mediated transactivation of hepatic Hamp (encoding the iron-regulatory hormone, hepcidin). In AI, high hepcidin represses iron absorption (and iron release from stores), thus lowering serum iron, and restricting iron for erythropoiesis (causing anemia). In less-severe disease states, inflammation may be limited to the intestine, but whether this perturbs iron homeostasis is uncertain. We hypothesized that localized gut inflammation will increase overall iron demand (to support the immune response and tissue repair), and that hepatic Hamp expression will decrease in response, thus derepressing (i.e., enhancing) iron absorption. Accordingly, we developed a rat model of mild, acute colitis, and studied iron absorption and homeostasis. Rats exposed (orally) to DSS (4%) for 7 days had intestinal (but not systemic) inflammation, and biomarker analyses demonstrated that iron utilization was elevated. Iron absorption was enhanced (by 2-3-fold) in DSS-treated, WT rats of both sexes, but unexpectedly, hepatic Hamp expression was not suppressed. Therefore, to gain a better understanding of regulation of iron absorption during acute colitis, Hamp KO rats were used for further experimentation. The severity of DSS-colitis was similar in Hamp KOs as in WT controls. In the KOs, increased iron requirements associated with the physiological response to colitis were satisfied by mobilizing hepatic storage iron, rather than by increasing absorption of enteral iron (as occurred in WT rats). In conclusion then, in both sexes and genotypes of rats, iron absorption was appropriately modulated to match physiological demand for dietary iron during acute intestinal inflammation, but regulatory mechanisms may not involve hepcidin.
登录
查看更多内容
影响因子：
4.3
作者：
Deugnier, Yves;Turlin, Bruno
通讯作者：
Turlin, Bruno
影响因子：
30.8
作者：
Kautz L;Jung G;Valore EV;Rivella S;Nemeth E;Ganz T
通讯作者：
Ganz T
DOI：
10.1016/j.jcmgh.2016.12.002
发表时间：
2017-05-01
影响因子：
7.2
作者：
Frazer, David M.;Wilkins, Sarah J.;Anderson, Gregory J.
通讯作者：
Anderson, Gregory J.
影响因子：
0.8
作者：
Klopfleisch, R.;Olias, P.
通讯作者：
Olias, P.
影响因子：
2.9
作者：
Koutroubakis IE;Ramos-Rivers C;Regueiro M;Koutroumpakis E;Click B;Schwartz M;Swoger J;Baidoo L;Hashash JG;Barrie A;Dunn MA;Binion DG
通讯作者：
Binion DG