Proteomic anatomy of human skin.

ABSTRACT

The extracellular matrix is composed of a variety of proteins which are essential for growth, wound healing, and fibrosis. It provides both structural support as well as contributing to the regulation of the local microenvironment. To further characterize the molecular composition of human skin we have undertaken a proteomic approach to identify proteins in three skin regions from two locations. Using laser microdissection, extracellular matrix was obtained from three distinct regions (basement membrane, papillary dermis, and reticular dermis) of formalin-fixed, paraffin embedded tissue from normal human leg and breast skin. The proteome of these regions was determined by mass spectrometric analysis. This study provides a relative quantitative assessment, including protein composition and relative abundance, of the proteins found in different skin regions giving rise to a "proteomic anatomy" of skin. Our findings indicate that there was little difference detected in the subproteomes of the dermal and papillary regions and little difference between the proteomes of leg skin compared to breast skin. One finding of interest is the identification of tenascin-X only in the breast dermis and serum amyloid P-component in the leg dermis. The results of this proteomic analysis corroborate much of the information on the protein composition identified by other methodologies found in the literature but provide additional insight as to localization of skin proteins in the various regions of skin. One potential outcome of this study is that identification of a more global proteomic composition in normal skin may serve as the basis for characterizing and comparing the skin proteomes from a variety of disease states, which may lead to a more complete understanding of the pathology of the disease as well as new therapeutic treatments. BIOLOGICAL SIGNIFICANCE: This investigation underscores the power of proteomics to bring semiquantitative, non-presumptive molecular characterization to the field of histological anatomy. Traditionally, anatomy relied on visual or histochemical structural characterization which generally involved some level of understanding of the area of interest. With the advent of laser microdissection or laser capture microscopy localization of anatomical structures of interest can be correlated to molecular composition by virtue of mass spectrometric determination of the proteome of that structure. One potential outcome of this study is that identification of a more global proteomic composition in normal skin may serve as the basis for characterizing and comparing the skin proteomes from a variety of disease states, which may lead to a more complete understanding of the pathology of the disease as well as new therapeutic treatments.