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. 2009 Sep;4(3):294-301.
doi: 10.1007/s11552-009-9164-0. Epub 2009 Jan 29.

Differential gene expression analysis of subcutaneous fat, fascia, and skin overlying a Dupuytren's disease nodule in comparison to control tissue

Barbara Shih  1 , Jason J Brown, Daniel J Armstrong, Tommy Lindau, Ardeshir Bayat
Affiliations

Differential gene expression analysis of subcutaneous fat, fascia, and skin overlying a Dupuytren's disease nodule in comparison to control tissue

Barbara Shih et al. Hand (N Y). 2009 Sep.

Abstract

Dupuytren's disease (DD) is a benign fibroproliferative tumor with an unknown etiology and high recurrence postsurgery. Several observations suggest the possible involvement of skin overlying nodule (SON) and the subcutaneous fat in the pathogenesis of DD. This study aims to (1) compare the gene expression levels of SON and subcutaneous fat in DD and normal subjects and (2) to compare transverse palmar fascia (Skoog's fibers) from DD patients as internal control tissue, with palmar fascia (transverse carpal ligament) from patients undergoing carpal tunnel release as external control. Skin, fat, and fascia were obtained from five DD patients of Caucasian origin (age = 66 +/- 14) and from five control subjects (age = 57 +/- 19) undergoing carpal tunnel release. Total ribonucleic acids was extracted from each sample and used for complementary deoxyribonucleic acid synthesis. Real-time quantitative polymerase chain reaction was used to assess the gene expression levels of six candidate genes: A disintegrin and metalloproteinase domain (ADAM12), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), iroquois homeoboxprotein 6 (IRX6), periostin, osteoblast specific factor, proteoglycan 4, and tenascin C. Using independent t test, ADAM12, ALDH1A1, and IRX6 expression levels in DD fats were significantly (p < 0.05) higher than those in the controls. There is no significant difference in the gene expression levels of all six genes when comparing disease and control fascia and skin. Interestingly, ADAM12 up-regulation has also been observed in several other fibrotic and proliferative disorders. In conclusion, this study demonstrates potential roles for subcutaneous fat in DD pathogenesis as well as supports the use of transverse palmar fascia as appropriate control tissues in DD research.

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Figures

Figure 1
Figure 1
Summary flowchart of the steps taken in the study. Summary of the steps taken in the study to determine whether there is differential gene expression levels for genes in DD and control skin, fat, and fascia [39]. Following the consent of all subjects selected for the study, relevant surgical procedures (dermofasciectomy for cases and carpal tunnel release for controls) were carried out, and biopsies of skin, fat and palmar fascia were obtained. The biopsy samples were subjected to RNA extraction, following which cDNA synthesis and quantitative PCR were carried out. Relative gene expression levels were determined using the formula image. ΔCT was determined by subtracting the threshold cycle of reference gene from those of target genes. Independent t tests were then carried out on relative gene expression levels to determine genes that are significantly (p < 0.05) differentially expressed. ADAM12 A disintegrin and metalloproteinase domain; ALDH1A1 aldehyde dehydrogenase 1 family member; IRX6 iroquois homeoboxprotein 6; PRG4 proteoglycan 4; TNC tenascin C; POSTN periostin, osteoblast specific factor; RPL32 ribosomal protein L32; GAPDH glyceraldehyde-3-phosphate dehydrogenase; ΔCT delta threshold cycle; PCR polymerase chain reactions; RNA ribonucleic acid; cDNA complementary deoxyribonucleic acid.
Figure 2
Figure 2
Tissues subjected to analysis in this study. a This figure demonstrates the palm of the hand of an individual affected with Dupuytren’s disease, where the overlying skin has been removed to demonstrate the position of the palmar fascia in relation to the disease and harvested samples as indicated. Skin overlying palmar nodule, subcutaneous fat adjacent to palmar nodule, and transverse palmar fascia (Skoog’s fibers) were obtained from Dupuytren’s disease patients. b This figure demonstrates the palm of the hand of a control subject, where the overlying skin has been removed to demonstrate the position of the palmar fascia harvested. Skin, palmar fascia (transverse carpal ligament), and fat were obtained from control subjects, individuals undergoing carpal tunnel release.
Figure 3
Figure 3
Relative gene expression in each sample. The relative gene expression levels, obtained by normalizing candidate gene expression levels to reference genes, were obtained from quantitative polymerase chain reactions. The dark-colored bars represent the data for Dupuytren’s disease samples, and the light colored bars represent the data for control samples. Statistically significant (p < 0.05) differential gene expression for ADAM12, ALDH1A1, and IRX6 were observed in DD fat, which are marked with asterisk in the graphs. ADAM12 A disintegrin and metalloproteinase domain; ALDH1A1 aldehyde dehydrogenase 1 family member; IRX6 iroquois homeoboxprotein 6; PRG4 proteoglycan 4; TNC tenascin C; POSTN periostin, osteoblast specific factor. The CT values for DD fascia (n = 4) were previously published in Shih et al. [39].
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