A serial analysis of gene expression in sun-damaged human skin.

To study the phenotypic changes in human skin associated with repeated sun exposure at the transcription level, we have undertaken a comparative serial analysis of gene expression of sun-damaged preauricular skin and sun-protected postauricular skin as well as sun-protected epidermis. Serial analyses of gene expression libraries, containing multiple mRNA-derived tag recombinants, were made to poly(A+)RNA isolated from human postauricular skin and preauricular skin, as well as epidermal nick biopsy samples. 5330 mRNA-derived cDNA tags from the postauricular serial analysis of gene expression library were sequenced and these tag sequences were compared to cDNA sequences identified from 5105 tags analyzed from a preauricular serial analysis of gene expression library. Of the total of 4742 different tags represented in both libraries we found 34 tags with at least a 4-fold difference of tag abundance between the libraries. Among the mRNAs with altered steady-state(1) levels in sun-damaged skin, we detected those encoding keratin 1, macrophage inhibitory factor, and calmodulin-like skin protein. In addition, a comparison of cDNA sequences identified in the serial analysis of gene expression libraries obtained from the epidermal biopsy samples (5257 cDNA tags) and from both full-thickness skin samples indicated that many genes with altered steady-state transcript levels upon sun exposure were expressed in epidermal keratinocytes. These results suggest a major role for the epidermis in the pathomechanism of largely dermal changes in chronically sun-exposed skin.