ADAMTSL6 contributes to the maintenance of elastic fibers in the papillary dermis and decreases during photoaging in human skin.

BACKGROUND

Human skin includes an elastic fiber system consisting of oxytalan, elaunin, and elastin fibers, which are classified based on their fibrillin microfibril and elastin contents. These fibers decrease or lose their function with aging and photoaging. A disintegrin-like and metalloprotease domain with thrombospondin type I motifs-like 6 (ADAMTSL6) is a fibrillin microfibril-associated component that promotes fibrillin microfibril formation.

OBJECTIVE

To investigate the contribution of ADAMTSL6 to the maintenance and aging/photoaging of dermal elastic fibers in human skin.

METHODS

ADAMTSL6, fibrillin-1, and elastin in papillary dermis of sun-protected buttock skin and sun-exposed eyelid skin were detected by immunohistochemistry, and the contribution of ADAMTSL6 to elastic fiber formation in dermal fibroblasts was investigated.

RESULTS

ADAMTSL6 colocalized with fibrillin-1 in oxytalan fibers and parts of elaunin fibers in the papillary dermis, but not in the reticular dermis, even when fibrillin-1 was present in the reticular dermis. Furthermore, ADAMTSL6 expression levels in eyelid skin decreased more markedly than in buttock skin with aging. Temporary knockdown of ADAMTSL6 expression by small interfering RNA in cultured dermal fibroblasts resulted in decreased expression of fibrillin-1, while stable knockdown of ADAMTSL6 by short hairpin RNA did not affect the deposition of fibrillin-1 but increased the expression and deposition of elastin in dermal fibroblast-derived matrix.

CONCLUSION

Our results suggest that ADAMTSL6 contributes to the maintenance of oxytalan and elaunin fibers in the papillary dermis, and decreases slightly with intrinsic aging, but more prominently with photoaging. Maintaining ADAMTSL6 expression may contribute to preservation of dermal elastic fiber architecture.