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Differential activation of signaling pathways by UVA and UVB radiation in normal human epidermal keratinocytes
Deeba N Syed1, Farrukh Afaq, Hasan Mukhtar
1Department of Dermatology, University of Wisconsin, Madison, WI, USA.
Abstract:
Ultraviolet (UV) radiation from the solar spectrum is a major etiological factor for many cutaneous pathologies including cancer. By understanding changes in cell signaling pathways induced by UVA and UVB, novel strategies for prevention and treatment of UV-related pathologies could be developed. However, much of the information in the literature from various laboratories cannot cross talk because of difficulties associated with the use of ill-defined light sources and physiologically irrelevant light dosimetry. Herein, we have assessed the effect of exposure of normal human epidermal keratinocytes (NHEK) to UVA (2 and 4 J cm(-2)) or UVB (20 and 40 mJ cm(-2)) radiation. Employing western blot analysis, we found that exposure of NHEK to UVB, but not UVA, phosphorylates JNK1/2 at Th(183)/Tyr(185), STAT3 at Ser(727) , AKT at Ser(473) and increases c-Fos expression, whereas exposure to UVA, but not UVB, phosphorylates AKT at Thr(308). UVB as well as UVA exposure leads to increased phosphorylation of (1) ERK1/2 at Th(202)/Tyr(204); (2) p38 at Th(180)/Tyr(204); (3) STAT3 at Tyr(705); (4) mTOR at Thr(2448); and (v) p70S6k at Thr(421) /Ser(424); enhanced expression of PI3K (p85) and c-jun; and nuclear translocation of NFκB proteins. These findings could be considered as a beginning for understanding the differential effects of UVA and UVB in the human skin and may have implications both with respect to risk assessment from exposure to solar UV radiation, and to target interventions against signaling events mediated by UVA and UVB.
Insights
Ultraviolet (UV) radiation, from UVA and UVB, impacts skin cell signaling pathways differently. Understanding these distinct effects on normal human epidermal keratinocytes (NHEK) can inform UV radiation risk assessment and targeted interventions.
Area of Science:
- Dermatology
- Molecular Biology
- Photobiology
Background:
- Solar ultraviolet (UV) radiation is a primary cause of skin diseases, including cancer.
- Understanding UV-induced cell signaling pathways is crucial for developing prevention and treatment strategies.
- Current research faces challenges due to inconsistent light sources and dosimetry, hindering data comparison.
Purpose of the Study:
- To investigate the differential effects of UVA and UVB radiation on cell signaling pathways in normal human epidermal keratinocytes (NHEK).
- To establish a foundation for understanding UV-A and UV-B specific molecular responses in human skin.
- To provide insights for improved UV radiation risk assessment and targeted therapeutic interventions.
Main Methods:
- Exposure of NHEK to specific doses of UVA (2 and 4 J cm(-2)) or UVB (20 and 40 mJ cm(-2)).
- Utilized western blot analysis to assess protein phosphorylation and expression levels.
- Examined the activation and nuclear translocation of key signaling proteins.
Main Results:
- UVB uniquely phosphorylated JNK1/2, STAT3 (Ser727), AKT (Ser473), and increased c-Fos.
- UVA uniquely phosphorylated AKT (Thr308).
- Both UVA and UVB induced phosphorylation of ERK1/2, p38, STAT3 (Tyr705), mTOR, and p70S6k; increased PI3K (p85) and c-jun expression; and caused NFκB nuclear translocation.
Conclusions:
- UVA and UVB radiation elicit distinct and overlapping signaling responses in human epidermal keratinocytes.
- These findings highlight the differential molecular impacts of UVA and UVB, crucial for understanding UV-related skin pathologies.
- The study provides a basis for developing targeted interventions against specific UV-induced signaling events.
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