Open Access Research article

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

Latha Satish1*, William A LaFramboise2, David B O'Gorman3, Sandra Johnson1, Benjamin Janto1, Bing Siang Gan3, Mark E Baratz4, Fen Z Hu15, J Christopher Post156, Garth D Ehrlich1567 and Sandeep Kathju15

Author Affiliations

1 Center for Genomic Sciences, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA, USA

2 Department of Pathology, University of Pittsburgh, PA, USA

3 Cell and Molecular Biology Laboratory of the Hand and Upper Limb Centre, London, Ontario, Canada

4 Division of Upper Extremity Surgery, Department of Orthopaedics, Allegheny General Hospital, Pittsburgh, PA, USA

5 Department of Microbiology and Immunology, Drexel University College of Medicine, Allegheny Campus, Pittsburgh, PA, USA

6 Department of Otolaryngology, Drexel University College of Medicine, Allegheny Campus, Pittsburgh, PA, USA

7 Department of Human Genetics, Drexel University College of Medicine, Allegheny Campus, Pittsburgh, PA, USA

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BMC Medical Genomics 2008, 1:10  doi:10.1186/1755-8794-1-10

Published: 23 April 2008

Abstract

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.