Radiation-induced differentiation of normal human skin fibroblasts.
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ABSTRACT:
PROVIDER: PRJNA616270 | ENA |
REPOSITORIES: ENA
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Project description:(1) Gene expression profiles during radiation-induced premature, terminal differentiation of exponentially growing progenitor fibroblasts to postmitotic functional cells after single dose (4 Gy) or two fractions (2×4 Gy). (2) Comparison with gene expression profile of confluent cells after fractionated irradiation with 3×4 Gy
2021-02-15 | GSE147733 | GEO
Project description:Background: Infrared A radiation (IRA 760-1440 nm) is a major component of solar radiation and, similar to ultraviolet (UV) radiation, causes photoaging of human skin by increasing the expression of matrixmetalloproteinase-1 (MMP-1) expression in human skin fibroblasts. This gene-regulatory effect resulted from the IRA induced activation of the pleiotropic MAPKinase ERK1/2 signaling pathway, indicating that the IRA response extends beyond MMP-1. In the present study we have therefore assessed the IRA-induced transcriptom in primary human skin fibroblasts. Results: Microarray analysis revealed 599 transcripts to be regulated by physiologically relevant doses of IRA in primary human skin fibroblasts. The IRA induced transcriptom differed from changes known to be induced by UVB or UVA radiation in the same cell type. IRA responsive genes include four categories: extracellular matrix, calcium homeostasis, stress signaling, and apoptosis. These results were confirmed by realtime PCR experiments analyzing thirteen of these genes representing these four categories. By means of chemical inhibitors of known signaling pathways we next show that besides ERK1/2, the p38-, JNK-, PI3K/AKT-, STAT3-, and IL-6 as well as calcium mediated signaling pathways are functionally involved in the IRA gene response and that a major part of it is triggered by mitochondrial, and to a lesser extent non-mitochondrial production of reactive oxygen species. Conclusion: This study identifies IRA radiation as a potent modulator of gene expression in human skin cells. The IRA response is specific and involves genes which are of critical importance for the homeostasis of human skin. Our data confirm the previous notion that IRA contributes to premature skin aging and indicate that further biological effects may result from IRA exposure of human skin.
2010-07-10 | GSE17046 | GEO
Project description:Background: Infrared A radiation (IRA 760-1440 nm) is a major component of solar radiation and, similar to ultraviolet (UV) radiation, causes photoaging of human skin by increasing the expression of matrixmetalloproteinase-1 (MMP-1) expression in human skin fibroblasts. This gene-regulatory effect resulted from the IRA induced activation of the pleiotropic MAPKinase ERK1/2 signaling pathway, indicating that the IRA response extends beyond MMP-1. In the present study we have therefore assessed the IRA-induced transcriptom in primary human skin fibroblasts. Results: Microarray analysis revealed 599 transcripts to be regulated by physiologically relevant doses of IRA in primary human skin fibroblasts. The IRA induced transcriptom differed from changes known to be induced by UVB or UVA radiation in the same cell type. IRA responsive genes include four categories: extracellular matrix, calcium homeostasis, stress signaling, and apoptosis. These results were confirmed by realtime PCR experiments analyzing thirteen of these genes representing these four categories. By means of chemical inhibitors of known signaling pathways we next show that besides ERK1/2, the p38-, JNK-, PI3K/AKT-, STAT3-, and IL-6 as well as calcium mediated signaling pathways are functionally involved in the IRA gene response and that a major part of it is triggered by mitochondrial, and to a lesser extent non-mitochondrial production of reactive oxygen species. Conclusion: This study identifies IRA radiation as a potent modulator of gene expression in human skin cells. The IRA response is specific and involves genes which are of critical importance for the homeostasis of human skin. Our data confirm the previous notion that IRA contributes to premature skin aging and indicate that further biological effects may result from IRA exposure of human skin. To identify genes differentially regulated after IRA irradiation we analyzed a set of nine independent samples pairs (IRA irradiated vs. sham irradiated), using human primary human dermal fibroblasts from three different donors (termed F1 to F3). Cells between passage number five to ten were exposed in vitro to a dose of 860 J/cm2 IRA. IRA irradiation lasted 40 min leading to a total dose of 860 J/cm2. The culture dishes were placed on a cooled plate connected to thermostated bath (Thermo Haake GmbH, Karlsruhe, Germany) to maintain temperatures below 37°C during IRA irradiation. For irradiation, medium was replaced by phosphate-buffered saline (37°C, Gibco). Control cells (sham) were held on a 37°C thermostated plate under similar conditions without irradiation. Following the treatment cells were cultivated for 24 hours with serum free MEM culture medium at 37°C.
2010-07-10 | E-GEOD-17046 | biostudies-arrayexpress
Project description:1. effect of radiation on transcription in normal and radiation sensitive primary human fibroblasts. 2. comparison of the basal transcription levels in normal and radiation sensitive primary human fibroblasts.
2006-06-01 | E-MEXP-512 | biostudies-arrayexpress
Project description:The study was designed to determine the differential gene expression between burn eschar- and normal skin-derived pericytes. A comparison was also made to determine the gene expression between normal skin pericytes and normal skin fibroblasts and (2) comparison of differential gene expression between burn eschar pericytes and normal normal skin fibroblasts
2020-03-02 | GSE140926 | GEO
Project description:Skin is usually exposed during human exposures to ionizing radiation, however there are few experiments that evaluate the radiation responsiveness of the cells of the epidermis (keratinocytes) and those of the dermis (fibroblasts) in the same studies. We evaluated the transcriptional responses of quiesent primary keratinocytes and fibroblasts from the same individual and compared them with quiescent keratinocytes and fibroblasts that were immortalized by human telomerase (hTert). The primary transcriptional responses to 10-500 cGy ionizing radiation were p53-mediated responses; however, we did identify distinct responses between the keratinocytes and the fibroblasts. Keywords: keratinocytes and fibroblasts - dose response to ionizing radiation
2009-05-31 | GSE14466 | GEO
Project description:The bystander effect from ionizing radiation consists of cellular responses generated from non-irradiated cells to the irradiation of their neighbors. The bystander effect is predominant at low doses and can lead to DNA damage and genomic instability in the affected cells. This non-targeted effect of radiation has received attention due to its potential implications for cancer therapy and radiation protection. Although studied extensively, a complete understanding of its molecular mechanism is the subject of ongoing research. While many studies have targeted specific factors which are suggested to be involved in the bystander effect, few have looked at whole genome gene expression in bystander cells. Furthermore, even fewer studies have looked at the expression in normal human cell lines. In this study, we have monitored transcriptional responses to γ-radiation in irradiated and bystander normal fibroblasts simultaneously using a genome-wide microarray approach. Bystander fibroblasts incubated in medium from irradiated cells, showed transient enrichment (less than 1.5 fold) in ribosome and oxidative phosphorylation pathways, and neurodegenerative disease pathways associated with mitochondrial dysfunctions. Bystander fibroblasts did not, however, display increases in oxidative stress, a phenomenon often linked with the radiation induced bystander effect. Total RNA was isolated from normal human fibroblasts irradiated with 2.0 Gy and fibroblasts incubated with medium from sham irradiated and irradiated cells 2 h after irradiation. RNA was isolated 4, 8 and 26 h after irradiation and there are 4 replicates for each sample for a total of 36 samples.
2010-12-03 | E-GEOD-25772 | biostudies-arrayexpress
Project description:The bystander effect from ionizing radiation consists of cellular responses generated from non-irradiated cells to the irradiation of their neighbors. The bystander effect can lead to DNA damage and genomic instability in the affected cells. This non-targeted effect of radiation has received attention due to its potential implications for cancer therapy and radiation protection. Although studied extensively, a complete understanding of its molecular mechanism is the subject of ongoing research. While many studies have targeted specific factors which are suggested to be involved in the bystander effect, few have looked at whole genome gene expression in bystander cells. Furthermore, even fewer studies have looked at the expression in normal human cell lines. In this study, we have monitored transcriptional responses to γ-radiation in irradiated and bystander normal fibroblasts simultaneously using a genome-wide microarray approach. In this study we have investigated the transcriptional response in F11hTERT fibroblasts irradiated with 2 Gy, 2 hours after irradiation.
2010-12-03 | GSE25772 | GEO
Project description:UV-induced 6-4PPs were mapped in normal human skin fibroblasts following 500J/m2 of UVC irradiation
2021-08-27 | GSE175590 | GEO
Project description:Background: Dupuytren’s disease (DD) is a fibro-proliferative disorder of unknown aetiology. Previous studies have implicated multiple WNT signalling genes/proteins in Dupuytren pathology, including WNT4. However, it is not yet clear whether WNT signalling dysregulation plays an important role in the initiation of the disease or progression. The aim of this study was to determine if loss of WNT4 expression triggered ‘Dupuytren-like’ changes in the transcriptome of healthy skin fibroblasts. Methods: Fibroblasts were isolated from the wrists of healthy adult males and from the wrists and disease cord tissue from males in a family positive for Dupuytren’s disease. Normal skin fibroblasts from healthy controls were treated with WNT4 siRNA and scrambled controls. RNASeq was used to analyse the transcriptomes of disease and non-disease fibroblasts from patients with Dupuytren’s as well as in siRNA treated and non-treated control fibroblasts. Results: Analysis of the transcriptomes from DD patient and normal skin fibroblasts showed significant differences, including in WNT4 expression. Downregulation of WNT4 in normal skin fibroblasts using siRNA led to ‘DD-like’ changes in the transcriptome. Conclusion: In people susceptible to DD WNT4 is downregulated even in non-fibrotic fibroblasts. Knockdown of WNT4 in normal fibroblasts led to changes that made cells ‘DD-like’. This study shows that WNT4 is down regulated in ‘non-disease’ cells, and that downregulating WNT4 in normal skin fibroblasts leads to widespread ‘DD like’ changes in the transcriptome, suggesting WNT4 downregulation is a key driver of DD.
2024-07-01 | GSE269317 | GEO