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首页> 外文期刊>BMC Medical Genomics >Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren's Contracture
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Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren's Contracture

机译：Dupuytren挛缩症患者成纤维细胞中差异表达基因的鉴定

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Dupuytren's contracture (DC) is the most common inherited connective tissue disease of humans and is hypothesized to be associated with aberrant wound healing of the palmar fascia. Fibroblasts and myofibroblasts are believed to play an important role in the genesis of DC and the fibroproliferation and contraction that are hallmarks of this disease. This study compares the gene expression profiles of fibroblasts isolated from DC patients and controls in an attempt to identify key genes whose regulation might be significantly altered in fibroblasts found within the palmar fascia of Dupuytren's patients. Total RNA isolated from diseased palmar fascia (DC) and normal palmar fascia (obtained during carpal tunnel release; 6 samples per group) was subjected to quantitative analyses using two different microarray platforms (GE Code Link? and Illumina?) to identify and validate differentially expressed genes. The data obtained was analyzed using The Significance Analysis of Microarrays (SAM) software through which we identified 69 and 40 differentially regulated gene transcripts using the CodeLink? and Illumina? platforms, respectively. The CodeLink? platform identified 18 upregulated and 51 downregulated genes. Using the Illumina? platform, 40 genes were identified as downregulated, eleven of which were identified by both platforms. Quantitative RT-PCR confirmed the downregulation of three high-interest candidate genes which are all components of the extracellular matrix: proteoglycan 4 (PRG4), fibulin-1 (FBLN-1) transcript variant D, and type XV collagen alpha 1 chain. Overall, our study has identified a variety of candidate genes that may be involved in the pathophysiology of Dupuytren's contracture and may ultimately serve as attractive molecular targets for alternative therapies.
机译：Dupuytren挛缩症（DC）是人类最常见的遗传性结缔组织疾病，据推测与掌筋膜的伤口愈合异常有关。据信成纤维细胞和成肌纤维细胞在DC的起源以及成纤维细胞增殖和收缩中起重要作用，DC是该疾病的标志。这项研究比较了从DC患者和对照中分离出的成纤维细胞的基因表达谱，以试图找出在Dupuytren患者手掌筋膜内发现的成纤维细胞中其调控可能发生显着改变的关键基因。使用两种不同的微阵列平台（GE Code Link™和Illumina™）对从患病的掌筋膜（DC）和正常掌筋膜（在腕管释放过程中获得;每组6个样品）中分离的总RNA进行定量分析，以鉴定和差异验证表达的基因。使用微阵列的重要性分析（SAM）软件分析获得的数据，通过该软件，我们使用CodeLink？识别了69和40个差异调控的基因转录本。和Illumina？平台。 CodeLink？该平台鉴定了18个上调基因和51个下调基因。使用Illumina？在这两个平台上，共有40个基因被下调，其中有11个基因被下调。定量RT-PCR证实了三个高关注候选基因的下调，它们都是细胞外基质的所有成分：蛋白聚糖4（PRG4），纤维蛋白1（FBLN-1）转录变体D和XV型胶原α1链。总的来说，我们的研究已经确定了可能与Dupuytren挛缩症的病理生理学有关的多种候选基因，它们最终可能成为替代疗法的诱人分子靶标。

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