Rays and arrays: the transcriptional program in the response of human epidermal keratinocytes to UVB illumination

Abstract

The epidermis, our first line of defense from ultraviolet (UV) light, bears the majority of photodamage, which results in skin thinning, wrinkling, keratosis, and malignancy. Hypothesizing that skin has specific mechanisms to protect itself and the organism from UV damage, we used DNA arrays to follow UV-caused gene expression changes in epidermal keratinocytes. Of the 6,800 genes examined, UV regulates the expression of at least 198. Three waves of changes in gene expression can be distinguished, 0.5-2, 4-8, and 16-24 h after illumination. The first contains transcription factors, signal transducing, and cytoskeletal proteins that change cell phenotype from a normal, fast-growing cell to an activated, paused cell. The second contains secreted growth factors, cytokines, and chemokines; keratinocytes, having changed their own physiology, alert the surrounding tissues to the UV damage. The third wave contains components of the cornified envelope, as keratinocytes enhance the epidermal protective covering and, simultaneously, terminally differentiate and die, removing a carcinogenic threat. UV also induces the expression of mitochondrial proteins that provide additional energy, and the enzymes that synthesize raw materials for DNA repair. Using a novel skin organ culture model, we demonstrated that the UV-induced changes detected in keratinocyte cultures also occur in human epidermis in vivo.

Epidermal Growth Factor Receptor Signaling Is Partially Responsible for the Increased Matrix Metalloproteinase-1 Expression in Ocular Epithelial Cells after UVB Radiation

“…Also expressed at late time points were markers of terminal differentiation and components of the cornified envelope such as involucrin. 55 The authors stated that this could be functionally beneficial because enhanced cornification may provide additional protection to the cell from the effects of UV. Although speculative, similar mechanisms may explain the UV-protective phenotype of the conjunctivalderived epithelial cell described in the present study.…”

Transcriptional profiles of unirradiated or UV-irradiated human cells expressing either the cancer-prone XPB/CS allele or the noncancer-prone XPB/TTD allele

“…The genome transcript UVB regulation was previously investigated in normal human keratinocytes for different times after irradiation (Li et al, 2001;Sesto et al, 2001). Recently, the UVC transcript modulation in normal human fibroblasts was also documented (Gentile et al, 2003).…”

Pathway-specific Profiling Identifies the NF-κB-dependent Tumor Necrosis Factor α-regulated Genes in Epidermal Keratinocytes

“…Human Keratinocyte Cultures and Cytokine Treatment-Human neonatal foreskin epidermal keratinocytes were first grown in a defined growth medium, KGM, supplemented with 2.5 ng/ml epidermal growth factor and 0.05 mg/ml bovine pituitary extract (keratinocyte-SFM; Invitrogen), as described (22,23). Third-passage keratinocytes were used at 50 -70% confluence, at which point we switched to KBM, the same medium but unsupplemented.…”