Dermatological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Biogerontology. 2012 Feb;13(1):37-48. doi: 10.1007/s10522-011-9332-9. Epub 2011 Apr 2.
Intrinsic ageing of the skin is a subtle process resulting in some degree of skin laxity. The dermal elastic fibre network imbues skin with the capacity to recoil and loss of this property contributes to an aged, wrinkled appearance. Whilst elastic fibres have a complex, composite structure which allows them to fulfil multiple roles, the effects of intrinsic ageing on their discrete molecular components has not previously been explored. In this study, we have used a microarray-based approach to perform a novel survey of the changes in gene expression that occur in components of cutaneous elastic fibres as a result of intrinsic ageing. Age-related changes in gene expression were validated at the mRNA and protein levels using quantitative real-time polymerase chain reaction (qPCR) and immunostaining, respectively. The microarray revealed that the majority of elastic fibre network components were unchanged with age. However, three differentially expressed genes were identified: latent TGFβ-binding protein (LTBP)-2 which was up-regulated with age (fold change +1.58, P = 0.041); LTBP3 (fold change -1.67, P = 0.025) and the lysyl oxidase-like enzyme (LOXL1, fold change -1.47, P = 0.008) which were both down-regulated with age. Although the changes in gene expression for LTBP3 were not confirmed by either qPCR or immunostaining, the expression and tissue deposition of both LTBP2 and LOXL1 were significantly enhanced in intrinsically aged skin. Whilst the functional implications of these altered expression profiles remains to be elucidated, LTBP2 and LOXL1 are thought to play important roles in controlling and maintaining elastic fibre deposition, assembly and structure via binding to fibulin-5. Consequently, any age-related perturbations in the expression of these components may have important consequences on remodelling of the extracellular matrix and hence on the mechanical properties of intrinsically aged skin.
皮肤的内在老化是一个微妙的过程，导致皮肤在一定程度上变得松弛。真皮弹性纤维网络赋予皮肤回弹的能力，而这种特性的丧失导致皮肤呈现出老化、起皱的外观。虽然弹性纤维具有复杂的复合结构，使其能够发挥多种作用，但内在老化对其离散分子成分的影响尚未被探索过。在这项研究中，我们使用基于微阵列的方法对内在老化导致皮肤弹性纤维成分的基因表达变化进行了一项新颖的调查。使用定量实时聚合酶链反应 (qPCR) 和免疫染色分别在 mRNA 和蛋白质水平上验证了与年龄相关的基因表达变化。微阵列显示，随着年龄的增长，大多数弹性纤维网络成分没有变化。然而，鉴定出三个差异表达的基因：Latent TGFβ-binding protein (LTBP)-2 随着年龄的增长而上调 (倍数变化+1.58，P=0.041)；LTBP3 (倍数变化-1.67，P=0.025) 和赖氨酰氧化酶样酶 (LOXL1，倍数变化-1.47，P=0.008)，两者都随着年龄的增长而下调。尽管 qPCR 或免疫染色都没有证实 LTBP3 的基因表达变化，但 LTBP2 和 LOXL1 的表达和组织沉积在内在老化的皮肤中显著增强。虽然这些改变的表达谱的功能意义仍有待阐明，但 LTBP2 和 LOXL1 被认为通过与纤维连接蛋白-5 结合，在控制和维持弹性纤维沉积、组装和结构方面发挥重要作用。因此，这些成分的表达随年龄相关的任何波动都可能对细胞外基质的重塑以及内在老化皮肤的机械性能产生重要影响。
