Abstract:
:The proliferative responses of cells to mitogens decrease during aging, and this may result from age-related defects in signal transduction in response to mitogens. In this study, we have investigated the age-related alteration of responses to epidermal growth factor (EGF) in cultured human keratinocytes that were senesced in vitro by repeated passage. The stimulation with EGF increased the DNA-binding activity of activator protein 1 (AP-1), an important transcription factor for cell proliferation, in young keratinocytes, whereas the binding activity showed little or slight change in the senescent cells. The induced DNA-binding activity of AP-1 in young cells was inhibited by PD 98059, an inhibitor of MEK, and partially inhibited by GF 109203X, an inhibitor of protein kinase C. Western blot analysis demonstrated that EGF induced dramatic increase in the phosphorylation of EGF receptor (EGFR) and extracellular signal-regulated kinases (ERK) in young cells, while this phosphorylation was much less profound in senescent cells. Finally, the application of EGF to young cells resulted in increased phosphorylation of Fra-2, a Fos protein component of the Jun/Fos heterodimer AP-1 complex. This EGF-induced Fra-2 phosphorylation was attenuated in senescent cells. Taken together, our study suggests that the signal transduction mediated by EGF/ERK pathway is altered in senescent human keratinocytes, and this change may be attributed, in part, to the decreased AP-1 transcription activity observed in senescent keratinocytes.
journal_name
Exp Dermatoljournal_title
Experimental dermatologyauthors
Shi B,Isseroff RRdoi
10.1111/j.0906-6705.2005.00317.xsubject
Has Abstractpub_date
2005-07-01 00:00:00pages
519-27issue
7eissn
0906-6705issn
1600-0625pii
EXD317journal_volume
14pub_type
杂志文章abstract::The therapeutic hypothesis proposed by Speeckaert and van Geel in this issue (1) is based on the dramatic effects of the new drugs targeting immune privilege checkpoints (PD1/PDL, CTLA4) in current advanced melanoma therapy as major inductors of vitiligo changes in the skin. Such striking clinical manifestations canno...
journal_title:Experimental dermatology
pub_type: 评论,杂志文章
doi:10.1111/exd.13128
更新日期:2017-07-01 00:00:00
abstract::Antimicrobial peptides and proteins (AMP) are highly active molecules with a broad-spectrum of microbicidal activity. Human beta-defensins (hBD)-2 and hBD-3 were initially isolated from psoriatic-scale extracts, and other AMP have been identified in high concentrations in psoriatic skin explaining the uncommonness of ...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/exd.12538
更新日期:2014-11-01 00:00:00
abstract::The role of angiogenesis in tumour growth and metastasis is well established. However, investigations of tumour microcirculation to date have used either biopsy material from human tumours, or animal models in vivo. We have studied the tumour microcirculation in vivo in human skin cancers using video-microscopy to exa...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.1999.tb00374.x
更新日期:1999-06-01 00:00:00
abstract::Given that metastasized melanoma is a fatal disease in most cases, it is tempting to develop strategies to a priori prevent metastasis. We have stimulated the pulmonary innate immune system by macrophage-activating lipopeptide-2 (MALP-2), a specific agonist at Toll-like receptor (TLR) 2/6, and investigated its impact ...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2011.01386.x
更新日期:2012-02-01 00:00:00
abstract::Acquisition of potent human dermal papilla (DP) cells that can induce hair follicle neogenesis is an overarching concern, and various approaches have been tried. In an attempt to solve the problem, we previously introduced the three-dimensional (3D) culture of human DP cells and observed de novo formation of hair foll...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.13234
更新日期:2017-02-01 00:00:00
abstract:BACKGROUND:In vivo reflectance confocal microscopy (RCM) represents a promising imaging tool that allows a non-invasive examination of skin morphology in real time at nearly histological resolution, showing microanatomical structures and individual cells. OBJECTIVES:The aim of our study was to evaluate the diagnostic ...
journal_title:Experimental dermatology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1600-0625.2008.00822.x
更新日期:2009-06-01 00:00:00
abstract::Psoriasis is an inflammatory skin disease often associated with obesity. The anti-inflammatory adipokine vaspin, a suggested serine proteinase inhibitor of the serpin family, is discussed as a new link between inflammation and obesity. Here, we demonstrate that - different from healthy controls - vaspin serum levels i...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/j.1600-0625.2012.01460.x
更新日期:2012-04-01 00:00:00
abstract::Despite as yet limited clinical effectiveness, dendritic cell (DC)-based immunotherapy remains a promising approach for the treatment of cancer, but requires further improvement in its immunostimulatory effectiveness. Potent anti-tumor immunity often depends on the induction of type 1 (T(H)1) immune responses. Therefo...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2008.00800.x
更新日期:2009-01-01 00:00:00
abstract::The present study was designed to examine the expression of proopiomelanocortin (POMC) and its related derivative peptide adrenocorticotropic hormone (ACTH) in murine derived Thy-1+ dendritic cells. Immunostaining using a polyclonal antibody specific to ACTH and parent POMC molecule indicated the presence of POMC and ...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.1995.tb00208.x
更新日期:1995-10-01 00:00:00
abstract::Hair follicle central isthmus is surrounded by dense nerve endings and terminal Schwann cells (TSCs), forming a specialized sensory structure called lanceolate complexes. Extracellular matrix protein EGFL6 expressed from epidermis has been found closely associated with lanceolate complexes and important for proper ali...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.14085
更新日期:2020-04-01 00:00:00
abstract::Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) i...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.14139
更新日期:2021-01-01 00:00:00
abstract::White adipose tissue is known to be involved in numerous physiological processes such as insulin-mediated functions, lipid and glucose metabolism, vascular changes and coagulation. These processes are mainly mediated by adipokines that are secreted either from adipocytes or cells of the stromal-vascular fraction of ad...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2011.01402.x
更新日期:2012-01-01 00:00:00
abstract::IL-15 has emerged as a potentially relevant target in the IL-17 response in psoriasis. However, its mechanism is poorly characterized in humans. IL-15 and IL-23 are constitutively expressed in the psoriatic lesion. Also, IL-15 is considered a susceptibility-associated gene in psoriasis, as are IL-23R, and HLACW6. Here...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.14113
更新日期:2020-05-31 00:00:00
abstract::The living, not-cornified part of the epidermis consists mainly of keratinocytes. The control mechanisms of proliferation and differentiation are only partly understood. Similarly, the influence of ionic channels of the cell membrane on the proliferation of keratinocytes remains unclear. Preliminary investigations poi...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1034/j.1600-0625.2000.009003219.x
更新日期:2000-06-01 00:00:00
abstract::A two-stage genomewide association (GWA) analysis was conducted to investigate the genetic factors influencing ultraviolet (UV)-induced skin pigmentation in Korean females after UV exposure. Previously, a GWA study evaluating ~500 000 single nucleotide polymorphisms (SNPs) in 99 Korean females identified eight SNPs th...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.12809
更新日期:2015-12-01 00:00:00
abstract::Recent advances in the molecular biology of the dermo-epidermal basement membrane zone have contributed greatly to our understanding of the etiopathogenetic pathways underlying mechanobullous disorders. Genetic linkage was established between the keratin gene clusters and epidermolysis bullosa simplex, and keratin mut...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0625.1992.tb00001.x
更新日期:1992-10-01 00:00:00
abstract::It is well known that the trigger for actinic keratosis (AK) mainly depends on UV exposure. We evaluated the effects of long-term use of sunscreen on the histopathological and dermoscopic changes of AK in aged patients. Eighteen months use of sunscreen produced no change in the number of actinic keratoses or the advan...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.13081
更新日期:2016-08-01 00:00:00
abstract::Rosacea is a skin inflammatory condition accompanied by cutaneous signs such as oedema, flushing, erythema, telangiectasia and pustules. Generally, rosacea is triggered by ultraviolet B (UVB) exposure. When exposed to UVB, skin epidermis thickens and produces elevated levels of pro-inflammatory cytokines, especially k...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.14115
更新日期:2020-05-20 00:00:00
abstract:BACKGROUND:Methylenetetrahydrofolate reductase (MTHFR) is involved in the formation of methyl donors, which contribute to DNA methylation. DNA methylation is an essential epigenetic feature playing a critical role in gene regulation and cellular differentiation. In addition, MTHFR activity affects plasma homocysteine l...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.2008.00713.x
更新日期:2008-09-01 00:00:00
abstract::The aim of the present study was to evaluate experimentally whether administration of recombinant (rh) vascular endothelial growth factor (VEGF) can protect skin flaps from necrosis and to study the optimum mode of rh-VEGF administration. We used rats to study the effects of local or systemic administration of rh-VEGF...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.0906-6705.2004.00220.x
更新日期:2004-11-01 00:00:00
abstract::Despite groundbreaking new treatments such as checkpoint inhibition and targeted therapy, the overall response and survival rates are limited in patients with metastatic melanoma. Here, we hypothesize that melatonin and its metabolites could be promising boosters of the efficacy of BRAF/MEK inhibitors in patients with...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.14144
更新日期:2020-09-01 00:00:00
abstract::We investigated the effects of a single dose of mouse interleukin-31 (IL-31) on scratching behaviour in comparison with spontaneous skin-lesion- or serotonin (5-HT)- induced scratching behaviour in NC/Nga and BALB/c mice. Intradermal (i.d.) injection of IL-31 caused a gradual increase in long-lasting scratching (LLS, ...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.12222
更新日期:2013-10-01 00:00:00
abstract::Basal cell carcinoma of the skin (BCC) is caused by constitutive activation of the Sonic hedgehog (Shh) pathway, mainly through mutations either in the Shh receptor Patched (PTCH) or in its co-receptor Smoothened (Smo). Inhibitors of this pathway that are currently in clinical trials inhibit Smo. However, mutations in...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.12016
更新日期:2012-11-01 00:00:00
abstract::Chronic exposure to ultraviolet (UV) radiation alters components of the skin. We previously reported that chronic low-dose UV irradiation induced wrinkle formation but did not significantly alter dermal components of hairless mice. In the present study, we examined whether the epidermal changes by UV irradiation could...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1034/j.1600-0625.12.s2.4.x
更新日期:2003-01-01 00:00:00
abstract::The potentially severe side effects of systemic corticosteroids and immunosuppressants used in Pemphigus vulgaris (PV) call for novel therapeutic approaches. In this context, pharmacological inhibition of major pathogenic signalling effectors represents a promising alternative. However, we have also shown that overinh...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/exd.13458
更新日期:2017-12-01 00:00:00
abstract::The role of adhesion molecules in the control of hair follicle (HF) morphogenesis, regression and cycling is still rather enigmatic. Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neona...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.1999.tb00377.x
更新日期:1999-08-01 00:00:00
abstract::Pemphigus vulgaris (PV) is a regulatory T cell (Treg)-associated autoimmune disease. Treg cells maintain immunosuppression by expressing the signature transcription factor FOXP3. MicroRNAs (miRNAs) have frequently emerged as regulators in Treg-mediated immunosuppression. We previously found that miR-338-3p was overexp...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.14111
更新日期:2020-05-09 00:00:00
abstract::CD4+ Foxp3+ regulatory T cells (Tregs) are suppressors of immune activation and play a crucial role in the maintenance of peripheral tolerance. Mutations of Foxp3 result in fatal autoimmunity in multiple organs, including the skin, in both humans and mice. Many studies have demonstrated the altered frequency and funct...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/exd.13535
更新日期:2019-06-01 00:00:00
abstract::Hair follicle heterogeneity may be regulated by distinct dermal papillae (DP) that represent mesenchymal lineages, which can be defined by Sox2 expression. However, it was recently shown that GFP expression in the Sox2: GFP+/- mouse model occurs in the DPs of all hair follicle types, challenging the idea that hair fol...
journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/exd.13396
更新日期:2017-11-01 00:00:00
abstract::In the last decades melanoma incidence has been increasing worldwide, while mortality remained on a high level. Until now, there is no suitable therapy for metastasized melanoma, which could lead to a significant increase in overall survival. Apoptosis deficiency is supposed to be a critical factor for therapy resista...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0625.2007.00655.x
更新日期:2008-01-01 00:00:00