Skin biological responses to urban pollution in an ex vivo model.

The skin epidermis is continuously exposed to external aggressions, including environmental pollution. The cosmetic industry must be able to offer dedicated products to fight the effects of pollutants on the skin. We set up an experimental model that exposed skin explants maintained in culture to a pollutant mixture. This mixture P representing urban pollution was designed on the basis of the French organization 'Air Parif' database. A chamber, called Pollubox®, was built to allow a controlled nebulization of P on the cultured human skin explants. We investigated ultrastructural morphology by transmission electron microscopy of high pressure frozen skin explants. A global transcriptomic analysis indicated that the pollutant mixture was able to induce relevant xenobiotic and antioxidant responses. Modulated detoxifying genes were further investigated by laser micro-dissection coupled to qPCR, and immunochemistry. Both approaches showed that P exposure correlated with overexpression of detoxifying genes and provoked skin physiological alterations down to the stratum basale. The model developed herein might be an efficient tool to study the effects of pollutants on skin as well as a powerful testing method to evaluate the efficacy of cosmetic products against pollution.

Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways.

BACKGROUND: Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined. OBJECTIVES: To identify biomarkers associated with AGA. METHODS: Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers. RESULTS: This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/ß-catenin and bone morphogenic protein/transforming growth factor-ß signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss. CONCLUSIONS: This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches.

From experimental design to functional gene networks: DNA microarray contribution to skin ageing research.

There is no doubt that the DNA microarray-based technology contributed to increase our knowledge of a wide range of processes. However, integrating genes into functional networks, rather than terms describing generic characteristics, remains an important challenge. The highly context-dependent function of a given gene and feedback mechanisms complexify greatly the interpretation of the data. Moreover, it is difficult to determine whether changes in gene expression are the result or the cause of pathologies or physiological events. In both cases, the difficulty relies on the involvement of processes that, at an early stage, can be protective and later on, deleterious because of their runaway. Each individual cell has its own transcription profile that determines its behaviour and its relationships with its neighbours. This is particularly true when a mechanism such as cell cycle is concerned. Another issue concerns the analyses from samples of different donors. Whereas the statistical tools lead to determine common features among groups, they tend to smooth the overall data and consequently, the selected values represent the 'tip of the iceberg'. There is a significant overlap in the set of genes identified in the different studies on skin ageing processes described in the present review. The reason of this overlap is because most of these genes belong to the basic machinery controlling cell growth and arrest. To get a more full picture of these processes, a hard work has still to be done to determine the precise mechanisms conferring the cell type specificity of ageing. Integrative biology applied to the huge amount of existing microarray data should fulfil gaps, through the characterization of additional actors accounting for the activation of specific signalling pathways at crossing points. Furthermore, computational tools have to be developed taking into account that expression values among similar groups may not vary 'by chance' but may reflect, along with other subtle changes, specific features of one given donor. Through a better stratification, these tools will allow to recover genes from the 'bottom of the iceberg'. Identifying these genes should contribute to understand how skin ages among individuals, thus paving the way for personalized skin care.

Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain.

Epidemiology has highlighted the links between season of birth, latitude and the prevalence of brain disorders such as multiple sclerosis and schizophrenia. In line with these data, we have hypothesized that "imprinting" with low prenatal vitamin D could contribute to the risk of these two brain disorders. Previously, we have shown that transient developmental hypovitaminosis D induces permanent changes in adult nervous system. The aim of this study was to examine the impact of prenatal hypovitaminosis D on gene expression in the adult rat brain. Vitamin D deficient female rats were mated with undeprived males and the offspring were fed with a control diet after birth. At Week 10, gene expression in the progeny's brain was compared with control animals using Affymetrix gene microarrays. Prenatal hypovitaminosis D causes a dramatic dysregulation of several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, post-translational modifications, synaptic plasticity and neurotransmission. A computational analysis of these data suggests that impaired synaptic network may be a consequence of mitochondrial dysfunction. Since disruptions of mitochondrial metabolism have been associated with both multiple sclerosis and schizophrenia, developmental vitamin D deficiency may be a heuristic animal model for the study of these two brain diseases.