Hope Heart Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
J Gerontol A Biol Sci Med Sci. 2011 Nov;66(11):1201-7. doi: 10.1093/gerona/glr137. Epub 2011 Aug 17.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare, progressive segmental premature aging disease that includes scleroderma-like skin, progressive joint contracture, and atherosclerosis. Affected individuals die prematurely of heart attacks or strokes. Extracellular matrix dysregulation is implicated as a factor in disease progression. We analyzed messenger RNA and protein levels for matrix metalloproteinases (MMPs)-2,-3, and -9 in HGPS primary human dermal fibroblasts using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and gelatin zymography. MMP-3 messenger RNA and protein levels decreased significantly with increasing donor age in HGPS fibroblasts but not in controls. MMP-2 messenger RNA also showed a donor age-dependent decrease in HGPS fibroblasts, but levels of secreted protein were unchanged. MMP-9 was similar in HGPS and control cultures. The decreased MMP-3 may represent a shift in the inherent extracellular matrix-degrading proteolytic balance in favor of matrix deposition in HGPS. This metalloproteinase has the potential to serve as a biomarker of therapeutic efficacy when assessing treatments for HGPS.
哈钦森-吉尔福德早衰综合征（HGPS）是一种罕见的、进行性的节段性过早衰老疾病，包括硬皮病样皮肤、进行性关节挛缩和动脉粥样硬化。受影响的个体因心脏病发作或中风而过早死亡。细胞外基质失调被认为是疾病进展的一个因素。我们使用实时聚合酶链反应、酶联免疫吸附试验和明胶酶谱法分析了 HGPS 原代人真皮成纤维细胞中基质金属蛋白酶（MMPs）-2、-3 和 -9 的信使 RNA 和蛋白水平。MMP-3 信使 RNA 和蛋白水平在 HGPS 成纤维细胞中随供体年龄的增加而显著降低，但在对照组中则没有。MMP-2 信使 RNA 在 HGPS 成纤维细胞中也表现出供体年龄依赖性降低，但分泌蛋白水平不变。MMP-9 在 HGPS 和对照培养物中相似。减少的 MMP-3 可能代表了固有细胞外基质降解蛋白酶平衡向基质沉积的转变，有利于 HGPS。这种金属蛋白酶有可能成为评估 HGPS 治疗效果的治疗效果的生物标志物。
