Clinical features of photodamaged human skin are associated with a reduction in collagen VII

Abstract

Chronically sun-exposed or photodamaged human skin is characterized by a number of clinical features, including wrinkles. However, little is known about the molecular mechanisms that underlie these features. We investigated the hypothesis that the mechanism of wrinkle formation may involve loss of anchoring fibrils, composed mainly of collagen VII, which are important in maintaining dermal-epidermal junction integrity. Ten volunteers with moderate to severe photodamage of dorsal forearm skin were recruited to the study. Using immunohistochemistry, transmission electron microscopy and in situ hybridization, we compared collagen VII protein and mRNA content of photodamaged forearm skin with that of sun-protected hip and upper inner arm skin from the same subjects. Numbers of anchoring fibrils per linear microns of basement membrane (mean +/- SEM) were significantly lower in photodamaged skin (1.79 +/- 0.10) as compared with sun-protected hip (2.28 +/- 0.11) and upper inner arm skin (2.21 +/- 0.10) (P < 0.01), and similarly keratinocyte expression of collagen VII mRNA, quantitated as number of positively stained keratinocytes per high power field, was significantly reduced in photodamaged skin (6.3 +/- 2.5) as compared with sun-protected hip (20.0 +/- 5.6) and upper inner arm skin (17.7 +/- 4.9) (P < 0.001). Semiquantitative assessment of immunohistochemical staining for collagen VII showed a non-significant reduction in photodamaged skin as compared with sun-protected skin. We propose that reduced content of collagen VII in photodamaged skin contributes to wrinkle formation by weakening the bond between the dermis and epidermis.

A cosmetic ‘anti-ageing’ product improves photoaged skin: a double-blind, randomized controlled trial

“…Photoaged skin has a different ECM morphology with solar elastosis—the deposition of dystrophic elastic fibres in the dermis—being a prominent histological feature 5. Photoaged dermis contains significantly reduced levels of collagen types I and III,6 fewer anchoring fibrils at the dermal–epidermal junction (DEJ; collagen VII)7 and loss of the fibrillin-rich microfibrillar architecture in the papillary dermis 8. These remodelled ageing phenotypes are thought in part to be due to increased cutaneous expression of matrix metalloproteinases (MMPs) 9–11…”

Over-the-counter anti-ageing topical agents and their ability to protect and repair photoaged skin

“…Reduced collagen VII anchoring fibrils beneath DEJ [5] Reduced tensile strength [6]. Increased wrinkle formation [5] Elastic-fibre network Accumulation of disorganised elastotic material in the reticular dermis [7] with a 'grentz zone' beneath the DEJ with a greatly reduced amount of fibrillinrich-microfibrils [8] Reduced elastic recoil [9]. Contributing factor to wrinkle development [10] GAG content Some studies suggest decreased HA content due to alterations in GAG binding ability [11].…”

“…Histologically, photoageing manifests with a thickening of the epidermis [3] and significant remodelling of the dermal extracellular matrix (ECM), which is thought to underlie clinical features such as wrinkles and loss of elastic recoil. During photoageing the three major classes of dermal ECM components -fibrillar collagens [1,[4][5][6], elastic fibres [7][8][9][10] and glycosaminoglycans (GAGs; both free and protein-associated) [11,12] -are differentially remodelled, leading to changes in their relative molecular composition, architecture and hence function ( Table 1). The most notable dermal changes are the early and specific loss of fibrillin-rich-microfibrils from the papillary dermis [8] followed by the subsequent loss of dermal collagen content [1,4], a build-up of dystrophic elastotic material within the deeper dermis [7,13,14] and an accumulation of disorganised GAGs, most notably chondroitin sulphate and hyaluronic acid (HA), in these areas of solar elastosis [12] (see Naylor et al [15] for comprehensive review of ECM turnover in instrinsic and photoaged skin).…”

Nonlinear elastic-viscoplastic constitutive equations for aging facial tissues

“…This modeling approach is justified at the histological level by tissue degradation processes. The dermis becomes atrophied during aging, with a reduction of the volume fraction of glycosaminoglicans (specifically, the hyaluronic acid) and collagen fibers of types I, III and VII (Craven et al 1997;Fleischmajer et al 1972). In particular, the dermal elastic fiber network (oxitalan fibers) decreases significantly with age (Cotta-Pereira et al 1978).…”

“…In particular, the dermal elastic fiber network (oxitalan fibers) decreases significantly with age (Cotta-Pereira et al 1978). In the face, these processes are accelerated by damage due to sunlight exposure (photoaging) and are complemented by solar elastosis, an accumulation of truncated, disorganized elastic fibers in the dermis (Craven et al 1997). Progressive atrophy of superficial fat occurs in the face at distinct locations (Donofrio 2000) which might contribute to the reduction of stiffness of the SMAS (Har-Shai et al 1998).…”