Alfonso-Rodríguez Camilo-Andrés, Garzón Ingrid, Garrido-Gómez Juan, Oliveira Ana-Celeste-Ximenes, Martín-Piedra Miguel-Ángel, Scionti Giuseppe, Carriel Víctor, Hernández-Cortés Pedro, Campos Antonio, Alaminos Miguel
Department of Histology (Tissue Engineering Group), University of Granada, Granada, Spain, and Instituto de Investigación Biosanitaria ibs, Granada, Spain; Ph.D. Programme in Biomedicine, University of Granada, Granada, Spain.
Department of Histology (Tissue Engineering Group), University of Granada, Granada, Spain, and Instituto de Investigación Biosanitaria ibs, Granada, Spain.
PLoS One. 2014 Nov 7;9(11):e112457. doi: 10.1371/journal.pone.0112457. eCollection 2014.
Dupuytren's disease is a fibro-proliferative disease characterized by a disorder of the extracellular matrix (ECM) and high myofibroblast proliferation. However, studies failed to determine if the whole palm fascia is affected by the disease. The objective of this study was to analyze several components of the extracellular matrix of three types of tissues-Dupuytren's diseased contracture cords (DDC), palmar fascia clinically unaffected by Dupuytren's disease contracture (NPF), and normal forehand fascia (NFF). Histological analysis, quantification of cells recultured from each type of tissue, mRNA microarrays and immunohistochemistry for smooth muscle actin (SMA), fibrillar ECM components and non-fibrillar ECM components were carried out. The results showed that DDC samples had abundant fibrosis with reticular fibers and few elastic fibers, high cell proliferation and myofibroblasts, laminin and glycoproteins, whereas NFF did not show any of these findings. Interestingly, NPF tissues had more cells showing myofibroblasts differentiation and more collagen and reticular fibers, laminin and glycoproteins than NFF, although at lower level than DDC, with similar elastic fibers than DDC. Immunohistochemical expression of decorin was high in DDC, whereas versican was highly expressed NFF, with no differences for aggrecan. Cluster analysis revealed that the global expression profile of NPF was very similar to DDC, and reculturing methods showed that cells corresponding to DDC tissues proliferated more actively than NPF, and NPF more actively than NFF. All these results suggest that NPF tissues may be affected, and that a modification of the therapeutic approach used for the treatment of Dupuytren's disease should be considered.
掌腱膜挛缩症是一种纤维增生性疾病,其特征在于细胞外基质(ECM)紊乱和肌成纤维细胞高度增殖。然而,研究未能确定整个掌腱膜是否受该疾病影响。本研究的目的是分析三种组织——掌腱膜挛缩症挛缩条索(DDC)、临床上未受掌腱膜挛缩症影响的掌腱膜(NPF)和正常前臂筋膜(NFF)——的细胞外基质的几个成分。进行了组织学分析、对每种组织重新培养的细胞进行定量、mRNA微阵列分析以及对平滑肌肌动蛋白(SMA)、纤维状ECM成分和非纤维状ECM成分进行免疫组织化学分析。结果表明,DDC样本有丰富的纤维化,伴有网状纤维且弹性纤维较少,细胞增殖和肌成纤维细胞、层粘连蛋白及糖蛋白含量高,而NFF未显示出这些特征中的任何一项。有趣的是,NPF组织中显示肌成纤维细胞分化的细胞更多,胶原蛋白、网状纤维、层粘连蛋白和糖蛋白也比NFF更多,尽管其水平低于DDC,弹性纤维与DDC相似。核心蛋白聚糖的免疫组织化学表达在DDC中较高,而多功能蛋白聚糖在NFF中高度表达,聚集蛋白聚糖无差异。聚类分析显示NPF的整体表达谱与DDC非常相似,重新培养方法表明,与DDC组织对应的细胞增殖比NPF更活跃,NPF比NFF更活跃。所有这些结果表明NPF组织可能受到影响,因此应考虑修改用于治疗掌腱膜挛缩症的治疗方法。