Differential expression of elastic fibre components in intrinsically aged skin

Abstract

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.