Deletion of the NR4A nuclear receptor NOR1 in hematopoietic stem cells reduces inflammation but not abdominal aortic aneurysm formation.
Deletion of the NR4A nuclear receptor NOR1 in hematopoietic stem cells reduces inflammation but not abdominal aortic aneurysm formation.
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DOI：
10.1186/s12872-017-0701-4
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发表时间：
2017-10-18
影响因子：
2.1
通讯作者：
Bruemmer D
中科院分区：
文献类型：
--
作者：
Qing H;Jones KL;Heywood EB;Lu H;Daugherty A;Bruemmer D
NR4A3孤儿核激素受体Nor1作为一种结构性活性转录因子，在病理性血管重塑过程中调节炎症、增殖和细胞生存。炎症过程是导致腹主动脉瘤(AAA)形成的关键机制。然而，Nor1在AAA形成中的作用以前还没有被研究过。从Nor1基因缺陷小鼠分离的骨髓来源的巨噬细胞中分析炎症基因的表达。低密度脂蛋白受体缺陷(LDLR−/−)小鼠接受照射后，取自Nor1−/−或野生型产仔鼠的造血干细胞进行重组。给动物注射血管紧张素II，并喂食富含饱和脂肪的食物以诱导AAA的形成。AAA的形成通过超声和体外测量进行量化。在分析的184个炎症基因中，有36个基因在内毒素处理的Nor1缺陷巨噬细胞中有差异调控。尽管在基因调控上存在差异，但在骨髓来源干细胞移植的LDLR缺陷小鼠中，造血干细胞中Nor1缺失并不影响AAA的形成。Nor1缺失可诱导巨噬细胞炎症基因的差异转录，但不影响小鼠AAA的形成。本文的在线版本(10.1186/s12872-0170701-4)包含向授权用户提供的补充材料。
The NR4A3 orphan nuclear hormone receptor, NOR1, functions as a constitutively active transcription factor to regulate inflammation, proliferation, and cell survival during pathological vascular remodeling. Inflammatory processes represent key mechanisms leading to abdominal aortic aneurysm (AAA) formation. However, a role of NOR1 in AAA formation has not been investigated previously. Inflammatory gene expression was analyzed in bone marrow-derived macrophages isolated from NOR1-deficient mice. Low-density lipoprotein receptor-deficient (LDLr−/−) mice were irradiated and reconstituted with hematopoietic stem cells obtained from NOR1−/− or wild-type littermate mice. Animals were infused with angiotensin II and fed a diet enriched in saturated fat to induce AAA formation. Quantification of AAA formation was performed by ultrasound and ex vivo measurements. Among 184 inflammatory genes that were analyzed, 36 genes were differentially regulated in LPS-treated NOR1-deficient macrophages. Albeit this difference in gene regulation, NOR1-deficiency in hematopoietic stem cells did not affect development of AAA formation in bone marrow-derived stem cell transplanted LDLr-deficient mice. NOR1 deletion induced differential inflammatory gene transcription in macrophages but did not influence AAA formation in mice. The online version of this article (10.1186/s12872-017-0701-4) contains supplementary material, which is available to authorized users.
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DOI：
10.1042/cs20090372
发表时间：
2010-03-09
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Daugherty A;Rateri DL;Charo IF;Owens AP;Howatt DA;Cassis LA
通讯作者：
Cassis LA
影响因子：
--
作者：
Pei, LM;Castrillo, A;Tontonoz, P
通讯作者：
Tontonoz, P
NOR-1/NR4A3调节血管细胞中细胞凋亡2（CIAP2）的细胞抑制剂：在对低氧应激的生存反应中的作用。
影响因子：
4.6
作者：
Alonso J;Galán M;Martí-Pàmies I;Romero JM;Camacho M;Rodríguez C;Martínez-González J
通讯作者：
Martínez-González J
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DOI：
10.1161/atvbaha.108.179705
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Libby P
通讯作者：
Libby P
DOI：
10.1161/01.atv.0000238346.84458.5d
发表时间：
2006-10-01
影响因子：
8.7
作者：
Bonta, Peter I.;van Tiel, Claudia M.;de Vries, Carlie J. M.
通讯作者：
de Vries, Carlie J. M.