Microarray-based identification of age-dependent differences in gene expression of human dermal fibroblasts

Dekker, Pim; Gunn, David A.; McBryan, Tony; Dirks, Roeland W.; Heemst, Diana van; Lim, Fei Ling; Jochemsen, Aart G.; Vries, Matty Verlaan-de; Nagel, Julia; Adams, Peter D.; Tanke, Hans J.; Westendorp, Rudi G. J.; Maier, Andrea B.

doi:10.1016/j.mad.2012.06.002

Cited by 16 publications

(12 citation statements)

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“…The number of age MAR genes is small compared to what has been reported for age related differential expression of genes in other tissues for example, in artery (3082 genes [4]) or blood (3287 genes [4] or 1497 genes [42]). But it is in the same order of magnitude as reported for skin (12 genes [4]) and dermal fibroblasts (104 genes [43]; In contrast, Glass et. al.…”

Section: Resultssupporting

confidence: 72%

Age, gender and UV-exposition related effects on gene expression in in vivo aged short term cultivated human dermal fibroblasts

et al. 2017

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Ageing, the progressive functional decline of virtually all tissues, affects numerous living organisms. Main phenotypic alterations of human skin during the ageing process include reduced skin thickness and elasticity which are related to extracellular matrix proteins. Dermal fibroblasts, the main source of extracellular fibrillar proteins, exhibit complex alterations during in vivo ageing and any of these are likely to be accompanied or caused by changes in gene expression. We investigated gene expression of short term cultivated in vivo aged human dermal fibroblasts using RNA-seq. Therefore, fibroblast samples derived from unaffected skin were obtained from 30 human donors. The donors were grouped by gender and age (Young: 19 to 25 years, Middle: 36 to 45 years, Old: 60 to 66 years). Two samples were taken from each donor, one from a sun-exposed and one from a sun-unexposed site. In our data, no consistently changed gene expression associated with donor age can be asserted. Instead, highly correlated expression of a small number of genes associated with transforming growth factor beta signalling was observed. Also, known gene expression alterations of in vivo aged dermal fibroblasts seem to be non-detectable in cultured fibroblasts.

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Section: Resultssupporting

confidence: 72%

Age, gender and UV-exposition related effects on gene expression in in vivo aged short term cultivated human dermal fibroblasts

et al. 2017

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“…Our analysis also highlighted concerted alteration of glutamate, polyamine and choline metabolisms as well as wnt/β-catenin and SDF-1/CXCL12 cascades. All these findings are generally consistent with previous studies of various ageing fibroblasts both in culture and in human cohorts [22–24]. This consistency prompts us to stress on the high quality of the dataset of Pazolli et al, 2009 being analyzed.…”

Section: Discussionsupporting

confidence: 90%

Pathways of aging: comparative analysis of gene signatures in replicative senescence and stress induced premature senescence

et al. 2016

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BackgroundIn culturing normal diploid cells, senescence may either happen naturally, in the form of replicative senescence, or it may be a consequence of external challenges such as oxidative stress. Here we present a comparative analysis aimed at reconstruction of molecular cascades specific for replicative (RS) and stressinduced senescence (SIPS) in human fibroblasts.ResultsAn involvement of caspase-3/keratin-18 pathway and serine/threonine kinase Aurora A/ MDM2 pathway was shared between RS and SIPS. Moreover, stromelysin/MMP3 and N-acetylglucosaminyltransferase enzyme MGAT1, which initiates the synthesis of hybrid and complex Nglycans, were identified as key orchestrating components in RS and SIPS, respectively. In RS only, Aurora-B driven cell cycle signaling was deregulated in concert with the suppression of anabolic branches of the fatty acids and estrogen metabolism. In SIPS, Aurora-B signaling is deprioritized, and the synthetic branches of cholesterol metabolism are upregulated, rather than downregulated. Moreover, in SIPS, proteasome/ubiquitin ligase pathways of protein degradation dominate the regulatory landscape. This picture indicates that SIPS proceeds in cells that are actively fighting stress which facilitates premature senescence while failing to completely activate the orderly program of RS. The promoters of genes differentially expressed in either RS or SIPS are unusually enriched by the binding sites for homeobox family proteins, with particular emphasis on HMX1, IRX2, HDX and HOXC13. Additionally, we identified Iroquois Homeobox 2 (IRX2) as a master regulator for the secretion of SPP1-encoded osteopontin, a stromal driver for tumor growth that is overexpressed by both RS and SIPS fibroblasts. The latter supports the hypothesis that senescence-specific de-repression of SPP1 aids in SIPS-dependent stromal activation.ConclusionsReanalysis of previously published experimental data is cost-effective approach for extraction of additional insignts into the functioning of biological systems.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3352-4) contains supplementary material, which is available to authorized users.

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“…Similarly to fibroblasts from patients with SSc, aged fibroblasts show reduced TGFβ expression and signal ling as well as increased Wnt-βcatenin signalling [139][140][141] . In mouse models of fibrosis, Wnt-βcatenin signalling downstream of TGFβ is partly responsible for the fibrotic response 142 .…”

Section: Systemic Sclerosismentioning

confidence: 99%

Autophagy: controlling cell fate in rheumatic diseases

2016

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Autophagy, an endogenous process necessary for the turnover of organelles, maintains cellular homeostasis and directs cell fate. Alterations to the regulation of autophagy contribute to the progression of various rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), osteoarthritis (OA) and systemic sclerosis (SSc). Implicit in the progression of these diseases are cell-type-specific responses to surrounding factors that alter autophagy: chondrocytes within articular cartilage show decreased autophagy in OA, leading to rapid cell death and cartilage degeneration; fibroblasts from patients with SSc have restricted autophagy, similar to that seen in aged dermal fibroblasts; fibroblast-like synoviocytes from RA joints show altered autophagy, which contributes to synovial hyperplasia; and dysregulation of autophagy in haematopoietic lineage cells alters their function and maturation in SLE. Various upstream mechanisms also contribute to these diseases by regulating autophagy as part of their signalling cascades. In this Review, we discuss the links between autophagy, immune responses, fibrosis and cellular fates as they relate to pathologies associated with rheumatic diseases. Therapies in clinical use, and in preclinical or clinical development, are also discussed in relation to their effects on autophagy in rheumatic diseases.

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Microarray-based identification of age-dependent differences in gene expression of human dermal fibroblasts

Cited by 16 publications

References 64 publications

Age, gender and UV-exposition related effects on gene expression in in vivo aged short term cultivated human dermal fibroblasts

Age, gender and UV-exposition related effects on gene expression in in vivo aged short term cultivated human dermal fibroblasts

Pathways of aging: comparative analysis of gene signatures in replicative senescence and stress induced premature senescence

Autophagy: controlling cell fate in rheumatic diseases

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