A transcriptomic analysis of the EK1.Br strain of human fibroblastoid keratocytes: The effects of growth, quiescence and senescence

Kipling, David; Jones, D. L.; Smith, Stephen W.; Giles, Peter; Jennert-Burston, Katrin; Ibrahim, Badr; Sheerin, Angela; Evans, Amy J. C.; Rhys-Willams, William; Faragher, R. G. A.

doi:10.1016/j.exer.2008.11.030

Cited by 17 publications

(16 citation statements)

References 23 publications

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“…Data on the proliferating, senescent and apoptotic fraction at each passage accompanies the analysed microarray data. This extends earlier studies reporting gene expression studies on senescence in other cell types, including fibroblasts, epithelial cells, endothelial cells and keratocytes (Shelton et al 1999, Chen et al 2004and Kipling et al, 2009. Differences in the expression profiles of senescent versus proliferating cells may provide insights into the potential role of senescent VSMCs cells in atherosclerosis.…”

Section: Introductionsupporting

confidence: 69%

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Microarray analysis of senescent vascular smooth muscle cells: A link to atherosclerosis and vascular calcification

Burton¹,

Giles²,

Sheerin³

et al. 2009

Experimental Gerontology

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International audienceLittle is known about the senescent phenotype of human vascular smooth muscle cells (VSMCs) and the potential involvement of senescent VSMCs in age-related vascular disease, such as atherosclerosis. As such, VSMCs were grown and characterised to generate senescent VSMCs needed for microarray analysis (Affymetrix). Comparative analysis of the transcriptome profiles of early (14 CPD) and late (39-42 CPD) passage VSMCs found a total of 327 probesets called as differentially expressed: 149 are up-regulated in senescence and 178 repressed (-value < 0.5%, minimum effect size of at least 2-fold differential regulation, explore data at www.madras.cf.ac.uk/vsmc). Data mining shows a differential regulation of genes at senescence associated with the development of atherosclerosis and vascular calcification. These included genes with roles in inflammation (IL1β, IL8, ICAM1, TNFAP3, ESM1 and CCL2), tissue remodelling (VEGF, VEGFβ, ADM and MMP14) and vascular calcification (MGP, BMP2, SPP1, OPG and DCN). The microarray data for IL1β, IL8 and MGP were validated by either, ELISA, Western blot analysis or RT-PCR. These data thus provide the first evidence for a role of VSMC senescence in the development of vascular calcification and provides further support for the involvement of senescent VSMCs in the progression of atherosclerosis

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Section: Introductionsupporting

confidence: 69%

“…The pro-inflammatory and tissue-degrading phenotype of VSMC is not a surprising one, as it appears to be a common feature of the senescent phenotype in multiple cell types, but is not necessarily a universal characteristic (Kipling et al, 2009). It was surprising however to see senescent VSMCs adopt a pro-calcificatory phenotype.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of senescent vascular smooth muscle cells: A link to atherosclerosis and vascular calcification

Burton¹,

Giles²,

Sheerin³

et al. 2009

Experimental Gerontology

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“…Rather, the amounts of SASP components released depend on cell context. For example, in senescent human fibroblastoid keratocytes in the eye, IL-6 is actually decreased (96). Studies are required to delineate upstream mechanisms causing the SASP, explore differences in the SASP among cell types, and elucidate the nature of the SASP in primary senescent cells in vivo rather than in cell culture.…”

Section: Figurementioning

confidence: 99%

Cellular senescence and the senescent secretory phenotype: therapeutic opportunities

Tchkonia¹,

Zhu²,

Deursen³

et al. 2013

J. Clin. Invest.

1,458

1,251

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Aging is the largest risk factor for most chronic diseases, which account for the majority of morbidity and health care expenditures in developed nations. New findings suggest that aging is a modifiable risk factor, and it may be feasible to delay age-related diseases as a group by modulating fundamental aging mechanisms. One such mechanism is cellular senescence, which can cause chronic inflammation through the senescence-associated secretory phenotype (SASP). We review the mechanisms that induce senescence and the SASP, their associations with chronic disease and frailty, therapeutic opportunities based on targeting senescent cells and the SASP, and potential paths to developing clinical interventions.

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“…The fibroblasts were grown on 13 mm diameter glass coverslips at identical seeding density to the parent culture. HCA2 neonatal foreskin fibroblasts (HCA2, a gift of Jim Smith, Houston, TX, USA) and Ek1.Br human ocular keratocytes (Kipling et al 2009) were cultured under identical conditions.…”

Section: Synthesis Of α β-Dihydroresveratrolmentioning

confidence: 99%

Resveratrol, but not dihydroresveratrol, induces premature senescence in primary human fibroblasts

Faragher

Burton

Majecha

et al. 2011

AGE

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Resveratrol, trans-3,5,4'-trihydroxystilbene, is a polyphenolic compound which has been reported to mimic the gene expression patterns seen in whole animals undergoing dietary restriction. The mechanism of action of resveratrol remains poorly understood, but modulation of both cellular proliferation and apoptosis has been proposed as important routes by which the molecule may exert its effects. This study reports the effects of both resveratrol and dihydroresveratrol (a primary in vivo metabolite) on the proliferative capacity of human primary fibroblasts. No generalised reduction in the growth fraction was observed when fibroblasts derived from three different tissues were treated with resveratrol at concentrations of 10 μm or less. However, concentrations above 25 μm produced a dose-dependent reduction in proliferation. This loss of the growth fraction was paralleled by an increase in the senescent fraction as determined by staining for senescence associated beta galactosidase and dose recovery studies conducted over a 7-day period. Entry into senescence in response to treatment with resveratrol could be blocked by a 30-min preincubation with the p38 MAP kinase inhibitor SB203580. No effects on proliferation were observed when cells were treated with dihydroresveratrol at concentrations of up to 100 μm.

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A transcriptomic analysis of the EK1.Br strain of human fibroblastoid keratocytes: The effects of growth, quiescence and senescence

Cited by 17 publications

References 23 publications

Microarray analysis of senescent vascular smooth muscle cells: A link to atherosclerosis and vascular calcification

Microarray analysis of senescent vascular smooth muscle cells: A link to atherosclerosis and vascular calcification

Cellular senescence and the senescent secretory phenotype: therapeutic opportunities

Resveratrol, but not dihydroresveratrol, induces premature senescence in primary human fibroblasts

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