Shih Barbara, Brown Jason J, Armstrong Daniel J, Lindau Tommy, Bayat Ardeshir
Plastic & Reconstructive Surgery Research, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK.
Hand (N Y). 2009 Sep;4(3):294-301. doi: 10.1007/s11552-009-9164-0. Epub 2009 Jan 29.
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.
掌腱膜挛缩症（DD）是一种病因不明且术后复发率高的良性纤维增生性肿瘤。多项观察结果表明，结节上方皮肤（SON）和皮下脂肪可能参与了DD的发病机制。本研究旨在：（1）比较DD患者与正常受试者SON和皮下脂肪的基因表达水平；（2）将DD患者的掌横筋膜（斯科格纤维）作为内部对照组织，与接受腕管松解术患者的掌筋膜（腕横韧带）作为外部对照进行比较。从5名白种人DD患者（年龄 = 66 ± 14岁）和5名接受腕管松解术的对照受试者（年龄 = 57 ± 19岁）获取皮肤、脂肪和筋膜。从每个样本中提取总核糖核酸并用于互补脱氧核糖核酸合成。采用实时定量聚合酶链反应评估6个候选基因的基因表达水平：解整合素和金属蛋白酶结构域（ADAM12）、醛脱氢酶1家族成员A1（ALDH1A1）、Iroquois同源盒蛋白6（IRX6）、骨膜蛋白、成骨细胞特异性因子、蛋白聚糖4和腱生蛋白C。使用独立t检验，DD脂肪中ADAM12、ALDH1A1和IRX6的表达水平显著高于对照组（p < 0.05）。比较疾病组和对照组的筋膜及皮肤时，所有6个基因的基因表达水平无显著差异。有趣的是，在其他几种纤维化和增殖性疾病中也观察到了ADAM12的上调。总之，本研究证明了皮下脂肪在DD发病机制中的潜在作用，并支持在DD研究中使用掌横筋膜作为合适的对照组织。
