Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren's Contracture

Abstract

<p>Abstract</p> <p>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.</p

Microarray Analysis of Dupuytren’s Disease Cells: The Profibrogenic Role of the TGF-� Inducible p38 MAPK Pathway

“…Our transcriptomics results revealed an over-expression of genes that code for important signalling proteins associated with the activation of TGF-β, abundantly expressed in DD [12,51], and the consequent ECM protein expression driven by p38 and Akt phosphorylation, namely THBS1, GADD45β and NUAK1 genes. Additionally, like previous studies, we found similar expression patterns of the ECM and myosin regulatory genes [25,31]. Our previously published proteomics results proved the pro�ibrogenic role of the phosphatidylinositol 3-kinase (PI3K)-Akt c-Jun N-terminal kinase signalling pathway in the onset of DD [30].…”

Radiotherapie in den Frühstadien des Morbus Dupuytren. Langzeitergebnisse nach 13 Jahren

“…(16) 17 (20) control both extracellular matrix remodeling and scar deposition, important processes regulating wound healing, which may be dysregulated in Dupuytren's contracture. Satish et al [27] compared the gene expression profiles of fibroblasts from patients and controls to find key genes whose regulation might be significantly altered. They found a downregulation of three genes, encoding for components of the extracellular matrix (proteoglycan 4, fibulin-I transcript variant D, and collagen α I type XV).…”

Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

“…Periostin has been shown to promote collagen fibrillogenesis and alter the deposition of ECM proteins in other systems [58] and larger scale microarray studies have identified COL1A1 mRNA, encoding the collagen α1 component of heterotrimeric and homotrimeric type-1 collagen [59], as up-regulated in DD cord [11,12]. Excess collagen deposition and changes in ECM components are established hallmarks of DD [11,[60][61][62] and collagen in DD cords has been previously reported to feature increased levels of hydroxylysine and reducible cross-links, features also evident in scar tissue and indicative of abnormal deposition [63]. As variations in collagen type can also regulate fibroblast-mediated contractility in vitro [64], it is possible that periostin may play a role in collagen production, fibrillogenesis and cross-linking in DD.…”