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The effect of acute and chronic photodamage on gene expression in human keratinocytes
M Garmyn1, H Degreef, B A Gilchrest
1Department of Dermatology, UZ Sint Rafael, Catholic University of Leuven, Belgium.
Abstract:
We identified genes involved in the normal response to acute UV damage, as they were modulated in cultured newborn keratinocytes by a single sublethal UV dose, appropriately filtered to mimic solar radiation. Their gene products encode proteins involved in the regulation of cell growth (proto-oncogenes c-myc and c-fos), a gene inducible by growth arrest and DNA damage (GADD153), the cytokine interleukin (IL) 1 alpha and beta and finally a differentiation-associated small proline-rich gene (SPR2). Because chronically sun-exposed skin is known to have altered immune responsiveness and a statistical predisposition to skin cancer, we then examined UV induction of these genes in cultured keratinocytes derived from habitually sun-exposed adult skin, and for the older donors in paired cultures derived from sun-protected site of the same donors. Aging alone increased the baseline expression of two differentiation-associated genes (SPR2 and IL-1 receptor antagonist) in cultures from sun-protected skin. In contrast, photoaging increased the UV inducibility of c-fos but decreased the baseline expression of the differentiation-associated genes IL-1 receptor antagonist and SPR2.
Insights
UV radiation impacts skin cell genes. Aging and sun exposure alter gene responses, affecting cell growth, DNA damage repair, and differentiation, potentially influencing skin cancer risk.
Area of Science:
- Molecular biology
- Dermatology
- Genetics
Background:
- Chronic sun exposure alters skin immune responses and increases skin cancer risk.
- UV radiation is a known carcinogen that damages skin cells.
- Keratinocytes are the primary cells in the epidermis and play a crucial role in skin's response to UV damage.
Purpose of the Study:
- To identify genes involved in the normal response to acute UV damage in keratinocytes.
- To investigate how aging and chronic sun exposure (photoaging) affect UV-induced gene expression in keratinocytes.
- To understand the molecular mechanisms underlying altered skin responsiveness in aged and photoaged skin.
Main Methods:
- Cultured newborn and adult human keratinocytes were exposed to a single sublethal dose of UV radiation mimicking solar radiation.
- Gene expression modulation was analyzed using techniques to identify specific genes and their products.
- Comparison of gene responses between keratinocytes from sun-protected and sun-exposed sites in older donors was performed.
Main Results:
- UV radiation modulated genes involved in cell growth (c-myc, c-fos), DNA damage response (GADD153), cytokine signaling (IL-1 alpha and beta), and differentiation (SPR2).
- Aging increased baseline expression of differentiation genes (SPR2, IL-1 receptor antagonist) in sun-protected skin.
- Photoaging enhanced UV inducibility of c-fos but decreased baseline expression of IL-1 receptor antagonist and SPR2 in adult skin.
Conclusions:
- UV radiation triggers a complex genetic response in keratinocytes involving cell growth, DNA repair, and differentiation pathways.
- Aging and photoaging significantly alter the baseline and UV-inducible gene expression patterns in skin keratinocytes.
- These alterations in gene regulation may contribute to the increased susceptibility to skin cancer observed in chronically sun-exposed and aged skin.