Elevated Matrix Metalloproteinases and Collagen Fragmentation in Photodamaged Human Skin: Impact of Altered Extracellular Matrix Microenvironment on Dermal Fibroblast Function

Exposure of the human skin to acute solar ultraviolet (UV) irradiation induces several members of the matrix metalloproteinase family (MMPs), which degrade collagen fibrils and other components of the dermal extracellular matrix (ECM) (Fisher et al., 1996; Yaar and Gilchrest, 2007). Elevation of MMPs due to chronic sun exposure can promote accumulation of dermal ECM fragmentation, which contributes to impaired skin function and aged appearance of chronically sun-exposed skin (Fisher et al., 1997). Histological and ultrastructural studies have revealed that major alterations in dermal extracellular matrix, most notably the accumulation of amorphous elastin-containing material in the upper dermis, and disorganized collagen fibrils, which constitute the bulk (90 % dry weight) of skin connective tissue. Elevation of MMPs and consequent dermal collagen fibril fragmentation following acute UV irradiation in human skin is well characterized (Fisher et al., 1996; Quan et al., 2009). However, expression of MMPs in clinically-photodamaged human skin and the role of fragmented collagen microenvironment in cellular function have not been extensively studied. Here we quantified gene expression of all 23 known mammalian MMPs (Egebla