Activation of an energy providing response in human keratinocytes after γ irradiation

Lamartine, Jérôme; Franco, Noreli; Minter, Pascale Le; Soularue, Pascal; Alibert, Olivier; Leplat, Jean Jacques; Gidrol, Xavier; Waksman, Gilles; Martin, Michèle

doi:10.1002/jcb.20394

Cited by 20 publications

(12 citation statements)

References 24 publications

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“…38 This study was approved by the ethical research committee ‘Comité de Protection des Personnes Sud-Est-II' (CODECOH Number DC-2008-262). A written informed consent was obtained from infants' parents according to the French bioethical law of 2004 (loi 94–654, 29/07/1994) and the guidelines of the Helsinki Declaration.…”

Section: Methodsmentioning

confidence: 99%

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Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes

et al. 2012

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The interfollicular epidermis is continuously renewed, thanks to a regulated balance between proliferation and differentiation. The ΔNp63 transcription factor has a key role in the control of this process. It has been shown that ΔNp63 directly regulates Runt-related transcription factor 1 (RUNX1) transcription factor expression in mouse keratinocytes. The present study showed for the first time that RUNX1 is expressed in normal human interfollicular epidermis and that its expression is tightly regulated during the transition from proliferation to differentiation. It demonstrated that ΔNp63 directly binds two different RUNX1 regulatory DNA sequences and modulates RUNX1 expression differentially in proliferative or differentiated human keratinocytes. It also showed that the regulation of RUNX1 expression by ΔNp63 is dependent on p53 and that this coregulation relies on differential binding and activation of RUNX1 regulatory sequences by ΔNp63 and p53. We also found that RUNX1 inhibits keratinocyte proliferation and activates directly the expression of KRT1, a critical actor in early keratinocyte differentiation. Finally, we described that RUNX1 expression, similar to ΔNp63 and p53, was strongly expressed and downregulated in basal cell carcinomas and squamous cell carcinomas respectively. Taken together, these data shed light on the importance of tight control of the functional interplay between ΔNp63 and p53 in regulating RUNX1 transcription factor expression for proper regulation of interfollicular epidermal homeostasis.

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Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry was done as previously described. 38 Antibodies are listed in Supplementary Table 3.…”

Section: Methodsmentioning

confidence: 99%

Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes

et al. 2012

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“…Some of the response pathways may reflect the particular cell types used or the use of established cell lines instead of primary tissue/cells. RNA expression in irradiated human fibroblasts (23, 24) and keratinocytes (25–27) has been examined previously. However, none of these studies included a side-by-side examination of radiation-induced gene expression in low-passage-number primary human fibroblasts and keratinocytes from the same patients.…”

Section: Introductionmentioning

confidence: 99%

Differential Gene Expression in Primary Human Skin Keratinocytes and Fibroblasts in Response to Ionizing Radiation

et al. 2009

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Although skin is usually exposed during human exposures to ionizing radiation, there have been no thorough examinations of the transcriptional response of skin fibroblasts and keratinocytes to radiation. The transcriptional response of quiescent primary fibroblasts and keratinocytes exposed to from 10 cGy to 5 Gy and collected 4 h after treatment was examined. RNA was isolated and examined by microarray analysis for changes in the levels of gene expression. Exposure to ionizing radiation altered the expression of 279 genes across both cell types. Changes in RNA expression could be arranged into three main categories: (1) changes in keratinocytes but not in fibroblasts, (2) changes in fibroblasts but not in keratinocytes, and (3) changes in both. All of these changes were primarily of p53 target genes. Similar radiation-induced changes were induced in immortalized fibroblasts or keratinocytes. In separate experiments, protein was collected and analyzed by Western blotting for expression of proteins observed in microarray experiments to be overexpressed at the mRNA level. Both Q-PCR and Western blot analysis experiments validated these transcription changes. Our results are consistent with changes in the expression of p53 target genes as indicating the magnitude of cell responses to ionizing radiation.

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“…Interestingly, when keratinocytes were exposed to gamma irradiation or x-rays, the transcriptional changes were similar to those found in the UV-treated cells (Koike, 2005;Lamartine, 2005). Specifically, the genes involved in cell energy metabolism appeared to be particularly responsive.…”

Section: Effects Of Uv and Other Environmental Stressmentioning

confidence: 53%

DNA Microarrays in Dermatology and Skin Biology

Blumenberg

2006

OMICS: A Journal of Integrative Biology

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Because of its accessibility, skin has been among the first organs analyzed using DNA microarrays. Skin cancers, melanomas, and basal and squamous cell carcinomas have been intensely investigated because they are very frequent and can be fatal. Psoriasis, one of the most common human inflammatory diseases, has been studied comprehensively using DNA microarrays. In addition, epidermal keratinocytes have been the target of many studies because they respond to a rich variety of inflammatory and immunomodulating cytokines, hormones, vitamins, ultraviolet (UV) light, toxins, and physical injury. Because of the ethical considerations, the effects of harmful or dangerous agents on skin have been studied using artificial skin substitutes. Transcriptional mechanisms that regulate epidermal differentiation and cornification have begun to yield their mysteries, and very exciting recent studies identified the genes specifically expressed in epidermal stem cells. Thus, skin has everything: stem cells, differentiation, signaling, inflammation, diseases, and cancer. All these exciting facets of skin have been explored using DNA microarrays. Researchers in skin biology and dermatology were among the first to implement this technology and we expect that they will continue to generate exciting and useful new knowledge.

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Activation of an energy providing response in human keratinocytes after γ irradiation

Cited by 20 publications

References 24 publications

Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes

Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes

Differential Gene Expression in Primary Human Skin Keratinocytes and Fibroblasts in Response to Ionizing Radiation

DNA Microarrays in Dermatology and Skin Biology

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