Genome-wide analysis using exon arrays demonstrates an important role for expression of extra-cellular matrix, fibrotic control and tissue remodelling genes in Dupuytren's disease.
Genome-wide analysis using exon arrays demonstrates an important role for expression of extra-cellular matrix, fibrotic control and tissue remodelling genes in Dupuytren's disease.
复制标题
DOI：
10.1371/journal.pone.0059056
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sprung CN
中科院分区：
文献类型：
--
作者：
Forrester HB;Temple-Smith P;Ham S;de Kretser D;Southwick G;Sprung CN
Dupuytren氏病（DD）是病理性纤维化的典型例子，它导致一种影响大部分人口的衰弱性疾病。其特征是成纤维细胞局部过度增殖，掌筋膜内胶原蛋白和其他细胞外基质成分（ECM）过量产生。纤维化逐渐导致掌筋膜和皮肤之间的结构挛缩，导致手指屈曲畸形或爪状，手部功能严重下降。虽然对DD的发病机制和手术治疗了解很多，但尽管经过多年的研究，对导致其发病和进展的因素知之甚少。目前，DD患者的基因表达模式为识别指导DD发病机制的基因提供了可能。在本研究中，我们使用从DD患者的纤维化组织切除活检中提取的成纤维细胞原代培养物，在全基因组基础上与正常对照成纤维细胞进行基因表达谱的比较。我们的研究已经确定了可能与DD发病机制有关的基因，包括一些与纤维化直接相关的基因。特别是，在DD患者样本中，三种基质金属肽酶（MMP1、MMP3、MMP16）、卵泡抑素和STAT1的表达水平显著降低，成纤维细胞生长因子（FGF9、FGF11）、一些胶原蛋白基因和其他ECM基因的表达水平显著升高。已知这些基因产物中有许多与纤维化、肿瘤形成和组织重塑的正常过程有关。此外，在一些DD相关基因中发现了选择性剪接。这些高度敏感的基因组研究为可能支持DD发生和进展的分子机制提供了新的见解。
Dupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD. In this study we used primary cultures of fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients to compare the gene expression profiles on a genome-wide basis with normal control fibroblasts. Our investigations have identified genes that may be involved with DD pathogenesis including some which are directly relevant to fibrosis. In particular, these include significantly reduced expression levels of three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and significantly increased expression levels of fibroblast growth factors (FGF9, FGF11), a number of collagen genes and other ECM genes in DD patient samples. Many of these gene products are known to be involved in fibrosis, tumour formation and in the normal processes of tissue remodelling. In addition, alternative splicing was identified in some DD associated genes. These highly sensitive genomic investigations provide new insight into the molecular mechanisms that may underpin the development and progression of DD.
登录
查看更多内容
影响因子：
2.3
作者：
Coleman, Stephen;Gilpin, David;Cohen, Brian
通讯作者：
Cohen, Brian
影响因子：
4.6
作者：
Desai, Shaunak S.;Hentz, Vincent R.
通讯作者：
Hentz, Vincent R.
影响因子：
7.2
作者：
Gudmundsson, KG;Arngrímsson, R;Jónsson, T
通讯作者：
Jónsson, T
影响因子：
64.5
作者：
BATTEGAY, EJ;RAINES, EW;ROSS, R
通讯作者：
ROSS, R
DOI：
10.1164/rccm.200412-1620oc
发表时间：
2005-09-15
影响因子：
24.7
作者：
Aoki, F;Kurabayashi, M;Kojima, I
通讯作者：
Kojima, I