Cell adhesion and matrix remodeling genes identified by co-expression analysis

Michael G. Walker, Wayne Volkmuth
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引用次数: 27

Abstract

Cell adhesion and matrix remodeling are elements in many diseases, ranging from atherosclerosis and fibrosis to metastatic cancer. However, many genes that participate in these processes have not yet been identified. To find such genes, we looked for previously uncharacterized genes that are co-expressed with known cell adhesion and matrix remodeling genes. The known genes in this study included MMP2, TIMP3, BM-40, chondroitin, connective tissue growth factor, fibromodulin, IGFBP5, laminin, MGP, myosin light chain kinase, several collagens, and other matrix and adhesion proteins. We found eight previously uncharacterized genes, here named MXRA1 through MXRA8, that were strongly co-expressed with these known adhesion and matrix genes. Five of the MXRA genes have a significant similarity to uncharacterized cDNA sequences or predicted proteins listed in the Genbank database, but otherwise show distant or no sequence similarity to genes with known function. Subsequent to our entry of the MXRA gene sequences in the Genbank, three of the eight genes have been independently described by other researchers: MXRA2 is α-parvin, a cell-matrix adhesion protein, MXRA4 is a C1 complement component receptor involved in cell adhesion, and MXRA5 is adlican, an adhesion proteoglycan. The analysis described here provides further evidence for the role of these genes in adhesion and matrix remodeling.

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通过共表达分析鉴定细胞粘附和基质重塑基因
细胞粘附和基质重塑是许多疾病的因素,从动脉粥样硬化、纤维化到转移性癌症。然而,许多参与这些过程的基因尚未被确定。为了找到这样的基因,我们寻找了以前未表征的基因,这些基因与已知的细胞粘附和基质重塑基因共表达。本研究中已知的基因包括MMP2、TIMP3、BM-40、软骨素、结缔组织生长因子、纤维调节素、IGFBP5、层粘连蛋白、MGP、肌球蛋白轻链激酶、几种胶原蛋白等基质和粘附蛋白。我们发现了8个以前未被鉴定的基因,这里命名为MXRA1到MXRA8,它们与这些已知的粘附和基质基因强烈共表达。其中5个MXRA基因与Genbank数据库中列出的未鉴定的cDNA序列或预测蛋白具有显著的相似性,但与已知功能的基因具有遥远或无序列相似性。在我们将MXRA基因序列输入Genbank之后,其他研究人员已经独立描述了八个基因中的三个:MXRA2是α-parvin,一种细胞基质粘附蛋白,MXRA4是参与细胞粘附的C1补体成分受体,MXRA5是adlican,一种粘附蛋白聚糖。本文所描述的分析为这些基因在粘附和基质重塑中的作用提供了进一步的证据。
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