Scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN) are hub genes of coexpression network modules associated with peripheral vein graft patency.
Scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN) are hub genes of coexpression network modules associated with peripheral vein graft patency.
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DOI：
10.1016/j.jvs.2014.12.052
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发表时间：
2016-07
影响因子：
4.3
通讯作者：
Clowes AW
中科院分区：
文献类型：
--
作者：
Kenagy RD;Civelek M;Kikuchi S;Chen L;Grieff A;Sobel M;Lusis AJ;Clowes AW
约30%的自体静脉移植物由于内膜增生或负性重塑而发生管腔狭窄和失败。我们以前发现，在体外，来自后来发展为狭窄的患者的静脉移植细胞比来自保持移植物通畅的患者的细胞对生长因子的反应更增殖。为了发现静脉移植物结果的新决定因素，我们使用系统生物学方法分析了这些细胞的基因表达谱，以基于其共表达模式将基因聚类成模块，并将结果与我们先前研究的生长数据以及迁移和基质重塑的新研究相关联。将来自4小时血清或PDGF-BB刺激的人隐静脉细胞（20个细胞系）的RNA用于基因表达的微阵列分析，随后进行加权基因共表达网络分析。还测定了响应于PDGF-BB的微趋化性室中的细胞迁移和响应于血清的细胞介导的胶原凝胶收缩。在对细胞进行生长或胶原凝胶收缩测定之前，使用siRNA抑制基因表达来测定基因功能。这些细胞来源于手术中获得的静脉移植物样品，并且这些旁路移植物的长期命运是已知的。迁移和细胞介导的胶原凝胶收缩均未显示与移植物结局相关。虽然分别有1，188和1，340个基因在血清和PDGF治疗后差异表达，但与保持通畅的移植物相比，从移植物狭窄患者中分离的细胞中没有单一基因差异表达。网络分析揭示了4个独特的基因组，我们称之为模块，与PDGF反应相关，和20个独特的模块与血清反应相关。分别来自PDGF和血清分析的“黄色”和“天蓝色”模块均与后期移植物狭窄相关（分别为P= 0.005和0.02）。在对PDGF的反应中，黄色也与增加的细胞生长有关。对于血清，天蓝色也与抑制胶原凝胶收缩有关。分别测试了Yellow和Skyblue（即与模块中其他基因连接最多的基因）、SCARA 5和SBSN的中枢基因对增殖和胶原收缩的影响。SCARA 5的敲低使增殖增加29.9 ± 7.8%（P<0.01），而SBSN的敲低没有影响。SBSN的敲除使胶原凝胶收缩增加24.2 ± 8.6%（P<0.05），而SCARA 5的敲除没有影响。使用加权基因共表达网络分析培养的静脉移植细胞基因表达，我们发现了两个小的基因模块，其中包括47个基因，与静脉移植失败。需要进一步的实验来描述在体内表达这些基因的静脉细胞以及这些基因在静脉移植物愈合中所起的作用，从模块中心基因SCARA 5和SBSN开始，这些基因已被证明对细胞增殖或胶原凝胶收缩具有适度的影响。
About 30% of autogenous vein grafts develop luminal narrowing and fail because of intimal hyperplasia or negative remodeling. We previously found that vein graft cells from patients that later develop stenosis proliferate more in vitro in response to growth factors than cells from patients that maintain patent grafts. To discover novel determinants of vein graft outcome we have analyzed gene expression profiles of these cells using a systems biology approach to cluster the genes into modules based on their co-expression patterns and to correlate the results with growth data from our prior study and with new studies of migration and matrix remodeling. RNA from 4 hour serum- or PDGF-BB-stimulated human saphenous vein cells obtained from the outer vein wall (20 cell lines), was used for microarray analysis of gene expression followed by weighted gene co-expression network analysis. Cell migration in microchemotaxis chambers in response to PDGF-BB and cell-mediated collagen gel contraction in response to serum were also determined. Gene function was determined using siRNA to inhibit gene expression before subjecting cells to growth or collagen gel contraction assays. These cells were derived from samples of the vein grafts obtained at surgery, and the long term fate of these bypass grafts was known. Neither migration nor cell-mediated collagen gel contraction showed a correlation with graft outcome. While 1,188 and 1,340 genes were differentially expressed in response to treatment with serum and PDGF, respectively, no single gene was differentially expressed in cells isolated from patients whose grafts stenosed compared to those that remained patent. Network analysis revealed 4 unique groups of genes, which we term modules, associated with PDGF responses, and 20 unique modules associated with serum responses. The “Yellow” and “Skyblue” modules, from PDGF and serum analyses respectively, both correlated with later graft stenosis (P=.005 and .02, respectively). In response to PDGF, Yellow was also associated with increased cell growth. For serum, Skyblue was also associated with inhibition of collagen gel contraction. The hub genes for Yellow and Skyblue (i.e. the gene most connected to other genes in the module), SCARA5 and SBSN, respectively, were tested for effects on proliferation and collagen contraction. Knockdown of SCARA5 increased proliferation by 29.9 ± 7.8% (P<.01), while knockdown of SBSN had no effect. Knockdown of SBSN increased collagen gel contraction by 24.2 ± 8.6% (P<.05), while knockdown of SCARA5 had no effect. Using weighted gene co-expression network analysis of cultured vein graft cell gene expression, we have discovered two small gene modules, which comprise 47 genes, that are associated with vein graft failure. Further experiments are needed to delineate the venous cells that express these genes in vivo and the roles these genes play in vein graft healing starting with the module hub genes SCARA5 and SBSN, which have been shown to have modest effects on cell proliferation or collagen gel contraction.
DOI：
10.1002/dvdy.24149
发表时间：
2014-09
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Galli LM;Szabo LA;Li L;Htaik YM;Onguka O;Burrus LW
通讯作者：
Burrus LW
影响因子：
3.7
作者：
Leclerc EA;Gazeilles L;Serre G;Guerrin M;Jonca N
通讯作者：
Jonca N
DOI：
10.4049/jimmunol.0903488
发表时间：
2010-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Yatherajam G;Banerjee PP;McCorkell KA;Solt LA;Hanson EP;Madge LA;Kang S;Worley PF;Orange JS;May MJ
通讯作者：
May MJ