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首页> 外文期刊>Cellular Physiology and Biochemistry >Microarray Analysis of Dupuytren's Disease Cells: The Profibrogenic Role of the TGF-p Inducible p38 MAPK Pathway
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Microarray Analysis of Dupuytren's Disease Cells: The Profibrogenic Role of the TGF-p Inducible p38 MAPK Pathway

机译：Dupuytren病细胞的微阵列分析：TGF-p诱导p38 MAPK途径的profibrogenic作用。

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Background: Dupuytren's disease (DD) is a nodular palmar fibromatosis that causes irreversible permanent contracture of fingers and results in the loss of hand function. Surgery still remains the only available solution for DD patients but cannot permanently cure the disease nor reduce high recurrence rates. With this rationale, we designed a study aimed at an improved understanding of the molecular mechanisms underlying DD. Our major focus was an analysis of the global gene expression profile and signalling pathways in DD cells with the aim of identifying novel biomarkers and/or therapeutic targets. Methods: Primary cells were cultured from surgically removed diseased and healthy tissue. Microarray expression analysis (HG-U133A array, Affymetrix) and qPCR was performed with total RNA isolated from primary DD cells. Mechanistic studies involving inhibition of pB8 phosphorylation were performed on normal human fibroblasts' and primary DD cells' in vitro models. Expression of stem cell markers in primary fibroblasts/myofibroblasts was assessed as well. Results: We identified 3 p38MAPK signalling pathway regulatory genes, THBS1, GADD45a and NUAK1, all involved in cellular proliferation and production of the extracellular matrix proteins. Inhibition of the p38MAPK signalling pathway induced down-regulation of myofibroblast markers, a-smooth muscle actin and palladin. A stem-cell like subpopulation positive for CD90 marker was identified among primary DD cells. Conclusion: The study reveals involvement of the p38 MAPK pathway as a possible signalling cascade in the pathogenesis of Dupuytren's disease. Moreover, a particular stem cell-like CD90+ subpopulation was identified that might contribute to DD development.
机译：背景：Dupuytren病（DD）是一种结节性手掌纤维瘤病，可导致手指不可逆的永久性挛缩并导致手功能丧失。手术仍然是DD患者唯一可用的解决方案，但不能永久治愈该疾病，也不能降低高复发率。根据这一原理，我们设计了一项研究，旨在更好地理解DD的分子机制。我们的主要重点是分析DD细胞中的全局基因表达谱和信号通路，以鉴定新型生物标志物和/或治疗靶标。方法：从手术切除的病变和健康组织中培养原代细胞。使用从原代DD细胞分离的总RNA进行微阵列表达分析（HG-U133A阵列，Affymetrix）和qPCR。在正常人成纤维细胞和原代DD细胞的体外模型中进行了涉及抑制pB8磷酸化的机制研究。还评估了干细胞标志物在原代成纤维细胞/成肌纤维细胞中的表达。结果：我们鉴定了3个p38MAPK信号通路调节基因THBS1，GADD45a和NUAK1，它们均参与细胞增殖和细胞外基质蛋白的产生。 p38MAPK信号通路的抑制诱导成肌纤维细胞标志物，α平滑肌肌动蛋白和帕拉丁的下调。在原代DD细胞中鉴定出CD90标记阳性的干细胞样亚群。结论：该研究揭示了p38 MAPK途径可能参与了Dupuytren病的发病过程中可能的信号级联反应。此外，确定了可能有助于DD发育的特定干细胞样CD90 +亚群。

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