ABSTRACT
BACKGROUND: Terrestrial ultraviolet (UV) radiation causes erythema, oxidative stress, DNA mutations and skin cancer. Skin can adapt to these adverse effects by DNA repair, apoptosis, keratinization and tanning. OBJECTIVES: To investigate the transcriptional response to fluorescent solar-simulated radiation (FSSR) in sun-sensitive human skin in vivo. METHODS: Seven healthy male volunteers were exposed to 0, 3 and 6 standard erythemal doses (SED). Skin biopsies were taken at 6 h and 24 h after exposure. Gene and microRNA expression were quantified with next generation sequencing. A set of candidate genes was validated by quantitative polymerase chain reaction (qPCR); and wavelength dependence was examined in other volunteers through microarrays. RESULTS: The number of differentially expressed genes increased with FSSR dose and decreased between 6 and 24 h. Six hours after 6 SED, 4071 genes were differentially expressed, but only 16 genes were affected at 24 h after 3 SED. Genes for apoptosis and keratinization were prominent at 6 h, whereas inflammation and immunoregulation genes were predominant at 24 h. Validation by qPCR confirmed the altered expression of nine genes detected under all conditions; genes related to DNA repair and apoptosis; immunity and inflammation; pigmentation; and vitamin D synthesis. In general, candidate genes also responded to UVA1 (340-400 nm) and/or UVB (300 nm), but with variations in wavelength dependence and peak expression time. Only four microRNAs were differentially expressed by FSSR. CONCLUSIONS: The UV radiation doses of this acute study are readily achieved daily during holidays in the sun, suggesting that the skin transcriptional profile of 'typical' holiday makers is markedly deregulated. What's already known about this topic? The skin's transcriptional profile underpins its adverse (i.e. inflammation) and adaptive molecular, cellular and clinical responses (i.e. tanning, hyperkeratosis) to solar ultraviolet radiation. Few studies have assessed microRNA and gene expression in vivo in humans, and there is a lack of information on dose, time and waveband effects. What does this study add? Acute doses of fluorescent solar-simulated radiation (FSSR), of similar magnitude to those received daily in holiday situations, markedly altered the skin's transcriptional profiles. The number of differentially expressed genes was FSSR-dose-dependent, reached a peak at 6 h and returned to baseline at 24 h. The initial transcriptional response involved apoptosis and keratinization, followed by inflammation and immune modulation. In these conditions, microRNA expression was less affected than gene expression.
Subject(s)
Skin Neoplasms , Ultraviolet Rays , Dose-Response Relationship, Radiation , Erythema/genetics , Humans , Male , Skin , Transcriptome , Ultraviolet Rays/adverse effectsABSTRACT
INTRODUCTION: In recent years several authors have proposed that muscle pathological changes in humans with dystrophin disorders and in mdx-mice are the result of regeneration attempts of this tissue subjected to constantly repeated bouts of necrosis. AIM: We compared morphological aspects of degenerative-regenerative groups observed in the mdx-mice with the regenerative phases that follow an intramuscular injection of 30 mL glycerol. MATERIALS AND METHODS: Gastrocnemius samples from mdx-mice, 1 to 5 months old and from glycerol injected C57Bl10/ScSn mice, 4 to 8 months old, were processed and analyzed in parallel. RESULTS: We were able to recognize degenerative-regenerative group stages in the mdx-mice that closely matched the anomalies found 1, 2, 3, 4-5, 7 and 21-28 days following the injection with glycerol. CONCLUSION. This study reinforces the hypothesis that muscle pathologic abnormalities of mdx-mice are the result of chronic muscle necrosis-regeneration. Morphologic mdx-mice degenerative-regenerative group staging will be a helpful tool for future investigation of muscle regeneration.
Subject(s)
Glycerol/pharmacology , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Regeneration/physiology , Animals , Female , Glycerol/therapeutic use , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Inbred mdx , Muscle, Skeletal/cytology , Muscle, Skeletal/physiology , Muscular Dystrophy, Animal/drug therapy , Muscular Dystrophy, Animal/pathologyABSTRACT
Introducción. En los últimos años, diversos autores han sugerido que los cambios patológicos musculares en los humanos con distrofinopatías y en los ratones mdx son el resultado de los intentos de regeneración realizados por este tejido sujeto a repetidas lesiones por necrosis. Objetivo. Se compararon los aspectos morfológicos de los grupos degenerativos-regenerativos observados en los ratones mdx y las fases regenerativas que se producen después de una inyección intramuscular de 30 µL de glicerol. Materiales y métodos. Se trataron y se analizaron unas muestras de gastrocnemio tomadas de ratones mdx, de 1 a 5 meses de edad, y de ratones C57Bl10/ScSn en los cuales se había inyectado glicerol, de 4 a 8 meses de edad. Resultados. Se reconocieron estadios en el grupo degenerativo-regenerativo en los ratones mdx que tenían una estrecha correspondencia con las anomalías halladas 1, 2, 3, 4-5, 7 y 21-28 días después de la inyección con glicerol. Conclusión. Este estudio corrobora la hipótesis de que las anomalías patológicas musculares de los ratones mdx son el resultado del proceso crónico de necrosis-regeneración muscular. La determinación del estadio morfológico del grupo degenerativoregenerativo de los ratones mdx será un instrumento valioso en futuras investigaciones (AU)
Introduction. In recent years several authors have proposed that muscle pathological changes in humans with dystrophin disorders and in mdx-mice are the result of regeneration attempts of this tissue subjected to constantly repeated bouts of necrosis. Aim. We compared morphological aspects of degenerative-regenerative groups observed in the mdx-mice with the regenerative phases that follow an intramuscular injection of 30µL glycerol. Materials and methods. Gastrocnemius samples from mdx-mice, 1 to 5 months old and from glycerol injected C57Bl10/ScSn mice, 4 to 8 months old, were processed and analyzed in parallel. Results. We were able to recognize degenerative-regenerative group stages in the mdx-mice that closely matched the anomalies found 1, 2, 3, 4-5, 7 and 21-28 days following the injection with glycerol. Conclusion. This study reinforces the hypothesis that muscle pathologic abnormalities of mdx-mice are the result of chronic muscle necrosisregeneration. Morphologic mdx-mice degenerative-regenerative group staging will be a helpful tool for future investigation of muscle regeneration (AU)
