Family with sequence similarity 5, member C (FAM5C) increases leukocyte adhesion molecules in vascular endothelial cells: implication in vascular inflammation.
Family with sequence similarity 5, member C (FAM5C) increases leukocyte adhesion molecules in vascular endothelial cells: implication in vascular inflammation.
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DOI：
10.1371/journal.pone.0107236
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rikitake Y
中科院分区：
文献类型：
--
作者：
Sato J;Kinugasa M;Satomi-Kobayashi S;Hatakeyama K;Knox AJ;Asada Y;Wierman ME;Hirata K;Rikitake Y
如果我们要了解导致动脉粥样硬化和随后的缺血性心脏病（包括急性心肌梗死）的分子机制，那么识别血管炎症的调节因子是重要的。序列相似性家族中的基因多态性5，成员C（FAM 5C）与急性心肌梗死风险增加相关，但人们对该基因产物在血管中的功能知之甚少。在此，我们报道了FAM 5C在内皮细胞中的表达和功能的调节。我们在这里显示，FAM 5C在体外和体内的内皮细胞中表达。免疫荧光显微镜显示FAM 5C定位于培养的人内皮细胞的高尔基体。冠状动脉连续切片免疫组化显示FAM 5C阳性内皮细胞表达细胞间粘附分子1（ICAM 1）或血管细胞粘附分子1（VCAM 1）。在培养的人内皮细胞中，FAM 5C的过表达增加了活性氧（ROS）的产生、核因子-κB（NF-κB）的活性以及ICAM-1、VCAM-1和E-selectin mRNA的表达，导致单核细胞粘附增强。FAM 5C在炎症刺激如TNF-α的反应中以NF-κB和JNK依赖的方式上调。通过小干扰RNA敲低FAM 5C抑制TNF-α诱导的ROS产生、NF-κB活性和这些白细胞粘附分子mRNA表达的增加，导致单核细胞粘附减少。这些结果表明，在内皮细胞中，当FAM 5C响应于炎症刺激而上调时，其通过增加ROS产生和NF-κB活性来增加白细胞粘附分子的表达。
Identification of the regulators of vascular inflammation is important if we are to understand the molecular mechanisms leading to atherosclerosis and consequent ischemic heart disease, including acute myocardial infarction. Gene polymorphisms in family with sequence similarity 5, member C (FAM5C) are associated with an increased risk of acute myocardial infarction, but little is known about the function of this gene product in blood vessels. Here, we report that the regulation of the expression and function of FAM5C in endothelial cells. We show here that FAM5C is expressed in endothelial cells in vitro and in vivo. Immunofluorescence microcopy showed localization of FAM5C in the Golgi in cultured human endothelial cells. Immunohistochemistry on serial sections of human coronary artery showed that FAM5C-positive endothelium expressed intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1). In cultured human endothelial cells, the overexpression of FAM5C increased the reactive oxygen species (ROS) production, nuclear factor-κB (NF-κB) activity and the expression of ICAM-1, VCAM-1 and E-selectin mRNAs, resulting in enhanced monocyte adhesion. FAM5C was upregulated in response to inflammatory stimuli, such as TNF-α, in an NF-κB- and JNK-dependent manner. Knockdown of FAM5C by small interfering RNA inhibited the increase in the TNF-α-induced production of ROS, NF-κB activity and expression of these leukocyte adhesion molecule mRNAs, resulting in reduced monocyte adhesion. These results suggest that in endothelial cells, when FAM5C is upregulated in response to inflammatory stimuli, it increases the expression of leukocyte adhesion molecules by increasing ROS production and NF-κB activity.
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FAM5C与心肌梗塞的遗传和功能关联。
影响因子：
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作者：
Connelly, Jessica J.;Shah, Svati H.;Doss, Jennifer F.;Gadson, Shera;Nelson, Sarah;Crosslin, David R.;Hale, A. Brent;Lou, Xuemei;Wang, Ty;Haynes, Carol;Seo, David;Crossman, David C.;Mooser, Vincent;Granger, Christopher B.;Jones, Christopher J. H.;Kraus, William E.;Hauser, Elizabeth R.;Gregory, Simon G.
通讯作者：
Gregory, Simon G.
DOI：
10.1161/atvbaha.111.244004
发表时间：
2012-04-01
影响因子：
8.7
作者：
Kurogane, Yusuke;Miyata, Muneaki;Rikitake, Yoshiyuki
通讯作者：
Rikitake, Yoshiyuki
影响因子：
20.1
作者：
Kinugasa, Mitsuo;Amano, Hisayuki;Rikitake, Yoshiyuki
通讯作者：
Rikitake, Yoshiyuki
影响因子：
4.2
作者：
Kuroiwa, Tsukasa;Yamamoto, Nobuharu;Shibahara, Takahiko
通讯作者：
Shibahara, Takahiko
影响因子：
15.9
作者：
Rajagopalan, S;Meng, XP;Galis, ZS
通讯作者：
Galis, ZS