Differential expression of extracellular matrix-mediated pathways in single-suture craniosynostosis.
Differential expression of extracellular matrix-mediated pathways in single-suture craniosynostosis.
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DOI：
10.1371/journal.pone.0026557
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Cunningham ML
中科院分区：
文献类型：
--
作者：
Stamper BD;Park SS;Beyer RP;Bammler TK;Farin FM;Mecham B;Cunningham ML
颅缝融合是一种由一条或多条颅缝过早融合而引起的疾病。单缝合性颅缝融合的发病机制复杂，虽然已确定了一些遗传生物标志物和环境易感性，但在许多病例中，其原因仍存在争议和不确定的原因。在这项研究中，1999例孤立性矢状面(n = 100)、单侧冠状(n = 50)和异位(n = 49)联会患者的基因表达数据与对照组(n = 50)以及彼此之间进行了比较。在控制了影响潜在偏差的变量后，Fgf7、sFRP4和VCAM1作为与单缝合骨融合相关的基因出现，因为它们的基因表达与对照人群相比发生了显著的变化。当比较所有单线缝合和对照病例时，通路分析暗示局部粘连和细胞外基质(ECM)-受体相互作用是不同调控的基因网络。最后，总体基因表达在冠状和异位病例之间被发现是高度保守的，事实证明Wnt2和IGFBP2是唯一在直接比较中显著地在很大程度上差异调节的基因。与成纤维细胞生长因子/胰岛素样生长因子/Wnt信号转导和细胞外基质介导的局灶性黏附相关的基因和基因网络的发现，不仅支持先前报道的与颅缝融合相关的生物标志物的参与，而且还引入了可能在颅缝融合发病机制中发挥关键作用的新的转录本和途径。
Craniosynostosis is a disease defined by premature fusion of one or more cranial sutures. The mechanistic pathology of single-suture craniosynostosis is complex and while a number of genetic biomarkers and environmental predispositions have been identified, in many cases the causes remain controversial and inconclusive. In this study, gene expression data from 199 patients with isolated sagittal (n = 100), unilateral coronal (n = 50), and metopic (n = 49) synostosis are compared against both a control population (n = 50), as well as each other. After controlling for variables contributing to potential bias, FGF7, SFRP4, and VCAM1 emerged as genes associated with single-suture craniosynostosis due to their significantly large changes in gene expression compared to the control population. Pathway analysis implicated focal adhesion and extracellular matrix (ECM)-receptor interaction as differentially regulated gene networks when comparing all cases of single-suture synostosis and controls. Lastly, overall gene expression was found to be highly conserved between coronal and metopic cases, as evidenced by the fact that WNT2 and IGFBP2 were the only genes differentially regulated to a significantly large extent in a direct comparison. The identification of genes and gene networks associated with Fgf/Igf/Wnt signaling and ECM-mediated focal adhesion not only support the involvement of biomarkers previously reported to be related to craniosynostosis, but also introduce novel transcripts and pathways that may play critical roles in its pathogenesis.
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影响因子：
3.5
作者：
Höflich, A;Lahm, H;Wolf, E
通讯作者：
Wolf, E
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
11.8
作者：
Day, TF;Guo, XZ;Yang, YZ
通讯作者：
Yang, YZ
影响因子：
5.7
作者：
Fanganiello, Roberto D.;Sertie, Andrea L.;Passos-Bueno, Maria Rita
通讯作者：
Passos-Bueno, Maria Rita