Department of Rheumatology, University Medical Centre Ljubljana, Vodnikova 62, Ljubljana 1000, Slovenia.
Arthritis Res Ther. 2012 May 1;14(3):R102. doi: 10.1186/ar3827.
Progressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses in vitro and in vivo. Reduced expression and function of PPAR-gamma in patients with SSc may contribute to progression of fibrosis. Here we evaluated the levels of adiponectin, a sensitive and specific index of PPAR-gamma activity, as a potential fibrogenic biomarker in SSc.
Adiponectin levels were determined in the sera of 129 patients with SSc and 86 healthy controls, and serial determinations were performed in 27 patients. Levels of adiponectin mRNA in skin biopsies from SSc patients were assessed in an expression profiling microarray dataset. Regulation of adiponectin gene expression in explanted human subcutaneous preadipocytes and fibroblasts was examined by real-time quantitative PCR.
Patients with diffuse cutaneous SSc had reduced serum adiponectin levels. A significant inverse correlation between adiponectin levels and the modified Rodnan skin score was observed. In longitudinal studies changes in serum adiponectin levels were inversely correlated with changes in skin fibrosis. Skin biopsies from a subset of SSc patients showed reduced adiponectin mRNA expression which was inversely correlated with the skin score. An agonist ligand of PPAR-gamma potently induced adiponectin expression in explanted mesenchymal cells in vitro.
Levels of adiponectin, reflecting PPAR-gamma activity, are correlated with skin fibrosis and might have potential utility as a biomarker in SSc.
系统性硬化症（SSc）中进行性纤维化与转化生长因子-β（TGF-β）信号的异常有关。过氧化物酶体增殖物激活受体γ（PPAR-γ）在体外和体内阻断成纤维细胞TGF-β反应。SSc 患者中 PPAR-γ的表达和功能降低可能导致纤维化进展。在这里，我们评估了脂联素的水平，作为 SSc 中潜在的纤维生成生物标志物，这是 PPAR-γ活性的一个敏感和特异的指标。
测定了 129 例 SSc 患者和 86 例健康对照者的血清脂联素水平，并对 27 例患者进行了系列测定。在 SSc 患者的皮肤活检标本的表达谱微阵列数据集中评估了脂联素 mRNA 水平。通过实时定量 PCR 研究了脂联素基因在体外分离的人皮下前脂肪细胞和成纤维细胞中的表达调控。
弥漫性皮肤 SSc 患者血清脂联素水平降低。脂联素水平与改良的 Rodnan 皮肤评分呈显著负相关。在纵向研究中，血清脂联素水平的变化与皮肤纤维化的变化呈负相关。SSc 患者的皮肤活检显示脂联素 mRNA 表达减少，与皮肤评分呈负相关。PPAR-γ激动剂配体在体外强烈诱导原代间充质细胞表达脂联素。
反映 PPAR-γ活性的脂联素水平与皮肤纤维化相关，可能作为 SSc 的一种潜在的生物标志物。
