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  • 1
    Keywords: EXPRESSION ; GROWTH-FACTOR ; IN-VIVO ; PHENOTYPE ; HUMAN EPIDERMIS ; REPLICATIVE SENESCENCE ; HUMAN-CELLS ; CELLULAR SENESCENCE ; INDUCED PREMATURE SENESCENCE ; INTERACTION NETWORKS
    Abstract: Most molecular hallmarks of cellular senescence have been identified in studies of cells aged in vitro by driving them into replicative or stress-induced senescence. Comparatively, less is known about the characteristic features of cells that have aged in vivo. Here we provide a systematic molecular analysis of normal human dermal fibroblasts (NHDFs) that were isolated from intrinsically aged human skin of young versus middle aged versus old donors. Intrinsically aged NHDFs in culture exhibited more frequently nuclear foci positive for p53 binding protein 1 and promyelocytic leukemia protein reminiscent of 'DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS)'. Formation of such foci was neither accompanied by increased DNA double strand breaks, nor decreased cell viability, nor telomere shortening. However, it was associated with the development of a secretory phenotype, indicating incipient cell senescence. By quantitative analysis of the entire secretome present in conditioned cell culture supernatant, combined with a multiplex cytokine determination, we identified 998 proteins secreted by intrinsically aged NHDFs in culture. Seventy of these proteins exhibited an age-dependent secretion pattern and were accordingly denoted 'skin aging-associated secreted proteins (SAASP)'. Systematic comparison of SAASP with the classical senescence-associated secretory phenotype (SASP) revealed that matrix degradation as well as proinflammatory processes are common aspects of both conditions. However, secretion of 27 proteins involved in the biological processes of 'metabolism' and 'adherens junction interactions' was unique for NHDFs isolated from intrinsically aged skin. In conclusion, fibroblasts isolated from intrinsically aged skin exhibit some, but not all, molecular hallmarks of cellular senescence. Most importantly, they secrete a unique pattern of proteins that is distinct from the canonical SASP and might reflect specific processes of skin aging.
    Type of Publication: Journal article published
    PubMed ID: 25815425
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  • 2
    ISSN: 1432-069X
    Keywords: Rhino mouse skin ; All-trans retinoic acid ; CD271 ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The histological and ultrastructural effects following 3 weeks' topical treatment with two agents (all-trans retinoic acid and a new synthetic retinoid-like substance, CD271) were evaluated on the epidermis and the epithelial wall of the pseudocomedones in rhino mouse skin. The comedolytic effects of these drugs were similar, and consisted of a reduction of the utricular diameter, with normalization of follicular units. Morphological examinations revealed a hyperplastic response with an increase in the number of cell layers of both epidermis and follicular epithelium, and modifications in keratinocyte differentiation. Ultrastructural changes in the epidermis and epithelial wall were observed mainly in the granular and horny layers, with increased desquamation, and a decrease in the cohesiveness of corneocytes. During the first week of treatment, some cutaneous toxic effects were noticed, but they normalized within two weeks. On the other hand, a fine granular material persisted in the intercellular spaces. It is confirmed that the skin of the rhino mouse is a good model for the evaluation of the comedolytic effects of drugs. Moreover, it reveals the specific effects of retinoids on epidermal differentiation. We have demonstrated that topically applied CD271 induces modifications similar to those obtained with all-trans retinoic acid. It is thus concluded that CD271 is a potentially effective anti-acne agent.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  For ethical and technical reasons, the in vivo biological effects of ultraviolet (UV) radiation on skin are difficult to study in human volunteers. The use of human skin grafted on to nude mice may circumvent this difficulty.Objectives  To investigate the effects of a single moderate UVB exposure on human skin grafted on to nude mice.Methods  Modifications of epidermal differentiation markers and patterns of keratin expression were assessed from 24 h to 14 days after a physiological UVB irradiation characterized by the induction of sunburn cells.Results  During the first 48 h postexposure, involucrin, loricrin, transglutaminase type I, filaggrin and keratin K2e expression were altered together with the formation of abnormal horny layers. Constitutive keratin K14 was increased while keratin K10 expression was delayed. Newly synthesized keratins K6, K16, K17 and K19 were induced in parallel with an increase in the epidermal proliferation rate. A progressive normalization of both keratinocyte proliferation and differentiation took place during the following days, reaching completion within 2 weeks.Conclusions  Exposure of human skin to a UVB dose corresponding to a mild sunburn reaction induces epidermal hyperproliferation and alterations of several constitutive differentiation markers, as well as a drastic modification in the pattern of epidermal keratins. Although these modifications were shown to be progressively reversed in a single exposure model, the data also suggest that subsequent UV exposures occurring during the recovery period may lead to potentially deleterious long-term consequences, such as photoageing and photocarcinogenesis. Grafted human skin appeared to be an attractive and promising model for investigating the biological consequences of UVB radiation in vivo.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sera from five patients with clinically and immunopathologically proven herpes gestationis were studied by complement fixing tmmunofluorescence and complement fixing immunoelectron microscopy using specimens of skin, amniochorion and placenta. The resutts demonstrated that the complement fixation antibody (herpes gestationis factor) could bind to the basement membrane zone of skin, amnion and chorion laeve but not to that of the placental syncytiotrophoblast. These data suggest that the herpes gestationis factor may be induced by the basement membrane zone antigens of extra-villous cytotrophoblasts.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Acute as well as chronic sun exposure induces biologically damaging effects in skin including photoageing and cancer. Ultraviolet (UV)A radiation is involved in this process; it is therefore important that sunscreen products provide efficient and stable protection in this range of wavelengths.Objectives  This study based on in vitro approaches was performed to demonstrate that photostability is an essential requirement to protect against UVA-induced genetic and dermal alterations.Methods  The protection afforded by two sunscreen products, differing with regard to their photostability, was studied using biological markers related to the genotoxic or photoageing impact of UVA or simulated solar UV radiation (UV-SSR). Comet assay was used to assess direct DNA breakage, photo-oxidized purines and lomefloxacin-induced DNA breaks in nuclei of normal human keratinocytes in culture. In similar conditions, detection of p53 accumulation was performed. The use of reconstructed skin in vitro allowed us to use a three-dimensional model to analyse the dermal and epidermal damage induced by UVA or UV-SSR exposure. Abnormal morphological features of the tissue as well as fibroblast alterations and matrix metalloproteinase-1 release induced by UV exposure have been studied after topical application of products on the skin surface.Results  The results showed that the photostable product afforded better protection with regard to all the criteria studied, compared with the photounstable product.Conclusions  These data demonstrate that the loss of absorbing efficiency within the UVA wavelength domain due to photoinstability may have detrimental consequences on cell function and lead to impairments that have been implicated in genotoxic events as well as in the photoageing process.
    Type of Medium: Electronic Resource
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