Cycling up the epidermis: reconciling 100 years of debate.

Abstract:

:There is likely general consensus within the skin research community that cell cycle control is critical to epidermal homeostasis and disease. The current predominant model proposes that keratinocytes switch off DNA replication and undergo cell cycle and cell growth arrest as they initiate terminal differentiation. However, this model cannot explain key physiological features of the skin, mainly why squamous differentiation prevails over proliferation in benign hyperproliferative disorders. In recent years, we have proposed an alternative model that involves mitotic slippage and endoreplication. This new model is controversial and has encountered resistance within the field. However, looking back at history, the epidermal cell cycle has been a matter of controversy and debate for around 100 years now. The accumulated data are confusing and contradictory. Our present model can explain and reconcile both old and new paradoxical observations. Here, we explain and discuss the endoreplicative cell cycle, the evidence for and against its existence in human epidermis and the important implications for skin homeostasis and disease. We show that regardless of the strengths or weaknesses of the Endoreplication Model, the existing evidence in support of the Cell Cycle Arrest Model is very weak.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Gandarillas A,Freije A

doi

10.1111/exd.12287

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

87-91

issue

2

eissn

0906-6705

issn

1600-0625

journal_volume

23

pub_type

杂志文章,评审
  • CD44 variant isoform v10 is expressed on tumor-infiltrating lymphocytes and mediates hyaluronan-independent heterotypic cell-cell adhesion to melanoma cells.

    abstract::CD44 is a family of cell-surface receptors on human lymphocytes that act as co-stimulatory molecules leading to the induction of effector functions in T cells. We have analyzed primary cutaneous malignant melanomas with clinical and histologic signs of tumor regression using immunohistochemistry and observed the predo...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1034/j.1600-0625.2003.00044.x

    authors: Weimann TK,Wagner C,Goos M,Wagner SN

    更新日期:2003-04-01 00:00:00

  • Interaction of peripheral nerves and mast cells, eosinophils, and basophils in the development of pruritus.

    abstract::Mast cells, eosinophils and basophils are central effector immune cells in allergic skin inflammation including atopic dermatitis (AD). Recent studies revealed that the bidirectional interaction between these three immune cell types (mast cells, eosinophils and basophils) and the nervous system is involved in the path...

    journal_title:Experimental dermatology

    pub_type: 杂志文章,评审

    doi:10.1111/exd.14014

    authors: Nakashima C,Ishida Y,Kitoh A,Otsuka A,Kabashima K

    更新日期:2019-12-01 00:00:00

  • Microdialysis of histamine in the skin of patients with mastocytosis.

    abstract::Mastocytosis represents a group of disorders characterized by the proliferation and accumulation of mast cells in tissue. The aim of the present study was to examine whether the interstitial histamine concentration in the skin is increased in mastocytosis patients and whether it correlates with the number of mast cell...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1034/j.1600-0625.2001.010002118.x

    authors: Krogstad AL,Roupe G

    更新日期:2001-04-01 00:00:00

  • R-Ras regulates vascular permeability, but not overall healing in skin wounds.

    abstract::Wounds close by keratinocytes migrating from the edge of the wound and re-epithelializing the epidermis. It has been proposed that the major stimuli for wound closure are blood-derived growth factors, chemokines and cytokines. The small GTPase R-Ras, a known integrin activator, also regulates vascular permeability dur...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.13851

    authors: Ketomäki T,Vähätupa M,May U,Pemmari T,Ruikka E,Hietamo J,Kaipiainen P,Barker H,Parkkila S,Uusitalo-Järvinen H,Järvinen TAH

    更新日期:2019-02-01 00:00:00

  • Advantages of histamine H4 receptor antagonist usage with H1 receptor antagonist for the treatment of murine allergic contact dermatitis.

    abstract::Histamine facilitates development of eczematous lesions in chronic allergic contact dermatitis. In addition to the well-known corticosteroid treatments, H1 receptor (H1R) antagonists also have been used. This study observed effects of histamine H4 receptor (H4R) antagonist usage with H1R antagonist in a murine chronic...

    journal_title:Experimental dermatology

    pub_type: 信件

    doi:10.1111/j.1600-0625.2012.01559.x

    authors: Matsushita A,Seike M,Okawa H,Kadawaki Y,Ohtsu H

    更新日期:2012-09-01 00:00:00

  • Chemiluminescent restriction fragment length polymorphism analysis (DNA fingerprinting) to identify keratinocytes from two donors in co-culture.

    abstract::The transplantation of allogeneic cells such as pancreatic islet cells, bone marrow, and keratinocytes for skin replacement is in growing use clinically. Present techniques which are used to distinguish transplanted allogeneic cells from phenotypically identical host cells in chimeric tissue have serious limitations. ...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.1993.tb00195.x

    authors: Young DM,Summers WC,Cuono CB

    更新日期:1993-02-01 00:00:00

  • Impairment of Th cell response in Card9 knockout mice with cutaneous mucormycosis caused by Rhizopus arrhizus.

    abstract::Card9 is a signalling adaptor protein in the downstream of many innate pattern recognition receptors (PRRs) and exerts a significant role in antifungal immunity. To date, Card9 deficiency has been reported to be related to increased susceptibility to many fungal infections. In this study, we established mucormycosis m...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.14020

    authors: Sun L,Wan Z,Li R,Yu J

    更新日期:2019-11-01 00:00:00

  • Detection of alpha- and beta-human papillomavirus (HPV) in cutaneous melanoma: a matched and controlled study using specific multiplex PCR combined with DNA microarray primer extension.

    abstract::There are few contradictory studies investigating the involvement of HPV in melanoma. We designed a controlled study to evaluate the HPV DNA prevalence in melanoma. One hundred patients with cutaneous malignant melanoma diagnosed between 2002 and 2006 were included. Complementary wide excision (healthy skin) was perfo...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2009.00866.x

    authors: Ruer JB,Pépin L,Gheit T,Vidal C,Kantelip B,Tommasino M,Prétet JL,Mougin C,Aubin F

    更新日期:2009-10-01 00:00:00

  • Highly pigmented Tg(Grm1) mouse melanoma develops non-pigmented melanoma cells in distant metastases.

    abstract::Murine model systems are critically required tools for the investigation of unknown mechanisms of melanoma development and metastasis and for developing more efficient therapies. The Tg(Grm1)EPv melanoma mouse model is characterized by spontaneous development of pigmented cutaneous melanomas at hairless skin regions, ...

    journal_title:Experimental dermatology

    pub_type: 信件

    doi:10.1111/j.1600-0625.2012.01560.x

    authors: Schiffner S,Chen S,Becker JC,Bosserhoff AK

    更新日期:2012-10-01 00:00:00

  • Serum amyloid A1 secreted from UV-irradiated keratinocytes induces matrix metalloproteinase-1 in fibroblasts through toll-like receptor 4.

    abstract::Ultraviolet (UV) irradiation on skin triggers photoageing-related phenotypes such as formation of wrinkles. UV ray upregulates matrix metalloproteinase-1 (MMP-1), which in turn degrades extracellular matrix proteins, mostly collagens. Serum amyloid A1 (SAA1) is an acute-phase protein of which plasma concentration incr...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12979

    authors: Han S,Jin SP,Oh JH,Seo EY,Park CH,Yoon HS,Lee DH,Chung JH

    更新日期:2016-07-01 00:00:00

  • Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis.

    abstract::Primary cutaneous large B-cell lymphomas, leg type (PCLBCL/LT) are primary cutaneous B-cell lymphoma (PCBCL) with an intermediate prognosis. Therefore, antracycline-based polychemotherapy combined with rituximab has been recommended as first-line treatment. Yet, despite this regimen, the 5-year survival rate remains 5...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12688

    authors: Teichert M,Stumpf C,Booken N,Wobser M,Nashan D,Hallermann C,Mogler C,Müller CS,Becker JC,Moritz RK,Andrulis M,Nicolay JP,Goerdt S,Thomas M,Klemke CD,Augustin HG,Felcht M

    更新日期:2015-06-01 00:00:00

  • Germline variation of the melanocortin-1 receptor does not explain shared risk for melanoma and thyroid cancer.

    abstract:BACKGROUND:Recently, germline variants of the melanocortin-1 receptor (MC1R) have been shown to be associated with an increased risk for BRAF mutant but not BRAF wild-type cutaneous melanoma. Similar to melanoma, BRAF mutations are also commonly found in papillary thyroid carcinomas. Furthermore, patients with melanoma...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2008.00827.x

    authors: Bauer J,Weng J,Kebebew E,Soares P,Trovisco V,Bastian BC

    更新日期:2009-06-01 00:00:00

  • Naringenin as an opener of mitochondrial potassium channels in dermal fibroblasts.

    abstract::Flavonoids belong to a large group of polyphenolic compounds that are widely present in plants. Certain flavonoids, including naringenin, have cytoprotective properties. Although the antioxidant effect has long been thought to be a crucial factor accounting for the cellular effects of flavonoids, mitochondrial channel...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.13903

    authors: Kampa RP,Kicinska A,Jarmuszkiewicz W,Pasikowska-Piwko M,Dolegowska B,Debowska R,Szewczyk A,Bednarczyk P

    更新日期:2019-05-01 00:00:00

  • Structural alterations provoked by narrow-band ultraviolet B in immortalized keratinocytes: assessment by atomic force microscopy.

    abstract::We applied atomic force microscopy (AFM) to visualize ultrastructural changes of the keratinocyte morphology after narrow-band ultraviolet B (NB-UVB) irradiation. Immortalized human keratinocytes were cultured under standard conditions, irradiated with NB-UVB light at doses ranging from 50 to 800 mJ/cm2 and imaged by ...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2007.00623.x

    authors: Reich A,Lehmann B,Meurer M,Muller DJ

    更新日期:2007-12-01 00:00:00

  • The potential role of c-Jun activation in patients with cutaneous lichen planus.

    abstract::c-Jun, a component of the activating protein-1 transcription factor family, has been known to play an important role in the control of cell proliferation. It is also suspected to be a critical mediator of tumor promotion. However, investigations of c-Jun activation patterns in inflammatory and inflammatory transformin...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2009.00965.x

    authors: Marceková Z,Flaig MJ,Kekus M,Ruzicka T,Rupec RA

    更新日期:2010-01-01 00:00:00

  • The antihistamines clemastine and desloratadine inhibit STAT3 and c-Myc activities and induce apoptosis in cutaneous T-cell lymphoma cell lines.

    abstract::Mycosis fungoides and its leukaemic counterpart Sézary syndrome are the most frequent cutaneous T-cell lymphomas (CTCL), and there is no cure for these diseases. We evaluated the effect of clinically approved antihistamines on the growth of CTCL cell lines. CTCL cell lines as well as blood lymphocytes from patients wi...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12086

    authors: Döbbeling U,Waeckerle-Men Y,Zabel F,Graf N,Kündig TM,Johansen P

    更新日期:2013-02-01 00:00:00

  • IL-24 is expressed during wound repair and inhibits TGFalpha-induced migration and proliferation of keratinocytes.

    abstract::Interleukin (IL)-24 is the protein product of melanoma differentiation-associated gene 7 (MDA-7). Originally identified as a tumor suppressor molecule, MDA-7 was renamed IL-24 and classified as a cytokine because of its chromosomal location in the IL-10 locus, its mRNA expression in leukocytes, and its secretory seque...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2010.01077.x

    authors: Poindexter NJ,Williams RR,Powis G,Jen E,Caudle AS,Chada S,Grimm EA

    更新日期:2010-08-01 00:00:00

  • Lesional Th17 cells and regulatory T cells in bullous pemphigoid.

    abstract::Th17 cells play crucial roles in the pathogenesis of autoimmune diseases. We previously reported that Th17 cells are recruited to the lesional skin in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The aim of this study was to evaluate lesional Th17 cells and Treg cells in bullous pemphigoid (BP). Correlations ...

    journal_title:Experimental dermatology

    pub_type: 信件

    doi:10.1111/j.1600-0625.2011.01378.x

    authors: Arakawa M,Dainichi T,Ishii N,Hamada T,Karashima T,Nakama T,Yasumoto S,Tsuruta D,Hashimoto T

    更新日期:2011-12-01 00:00:00

  • The single-chain anti-TNF-α antibody DLX105 induces clinical and biomarker responses upon local administration in patients with chronic plaque-type psoriasis.

    abstract::It is not clear whether TNF-α antagonists used in the treatment of psoriasis need to act systemically, or whether local inhibition of skin-produced TNF-α would be sufficient to silence skin inflammation. To answer this question, we conducted two multicentre, double-blinded, randomized, placebo-controlled clinical tria...

    journal_title:Experimental dermatology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1111/exd.12927

    authors: Tsianakas A,Brunner PM,Ghoreschi K,Berger C,Loser K,Röcken M,Stingl G,Luger T,Jung T

    更新日期:2016-06-01 00:00:00

  • Protein kinase A activation inhibits oncogenic Sonic hedgehog signalling and suppresses basal cell carcinoma of the skin.

    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

    authors: Makinodan E,Marneros AG

    更新日期:2012-11-01 00:00:00

  • A large conductance [Ca(2+)](i)-independent K(+) channel expressed in HaCaT keratinocytes.

    abstract::Patch-clamp recordings were carried out in the inside-out configuration in human keratinocytes of the cell line HaCaT. Patch pipettes were filled with 150 mM KCl, 1 mM CaCl(2) and 10 mM HEPES. In symmetrical KCl solutions, single channel currents from a large conductance channel (about 170 pS) were measured. Replaceme...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1034/j.1600-0625.2002.110405.x

    authors: Nguyen VH,Markwardt F

    更新日期:2002-08-01 00:00:00

  • Keratinocytes and dermal factors activate CRABP-I in melanocytes.

    abstract::Recognition that cellular retinoic acid binding protein (CRABP)-I and CRABP-II are found in different cell types has provided additional support for the presumably divergent roles of these two proteins in mediating retinoic acid (RA) effects in human skin. CRABP-II is expressed in fibroblasts and keratinocytes, and CR...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.1998.tb00337.x

    authors: Sanquer S,Reenstra WR,Eller MS,Gilchrest BA

    更新日期:1998-12-01 00:00:00

  • Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas.

    abstract::Epidermal growth factor receptor (EGFR) gene amplification and protein overexpression are common in several cancers. EGFR status has seldom been studied in cutaneous squamous carcinomas (SCCs), or their precursors, actinic keratoses (AKs). We evaluated the presence of EGFR genomic aberrations and EGFR protein overexpr...

    journal_title:Experimental dermatology

    pub_type: 信件

    doi:10.1111/j.1600-0625.2009.01028.x

    authors: Toll A,Salgado R,Yébenes M,Martín-Ezquerra G,Gilaberte M,Baró T,Solé F,Alameda F,Espinet B,Pujol RM

    更新日期:2010-02-01 00:00:00

  • Identification of a novel mutation in keratin 1 in a family with epidermolytic hyperkeratosis.

    abstract::Epidermolytic hyperkeratosis (EHK) is a hereditary skin disorder typified by blistering due to cytolysis. One in 100,000 individuals is affected by this autosomal-dominant disease. The onset of the disease phenotype is typically at birth. Histological and ultrastructural examination of the epidermis shows a thickened ...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1034/j.1600-0625.2000.009001016.x

    authors: Arin MJ,Longley MA,Epstein EH Jr,Rothnagel JA,Roop DR

    更新日期:2000-02-01 00:00:00

  • Variable Bax antigenicity is linked to keratinocyte position within epidermal strata and UV-induced apoptosis.

    abstract::Pro- and anti-apoptotic members of the Bcl-2 family are fundamental in the control of apoptosis. Among them, Bax plays a key role in apoptosis induction by mediating the release of apoptogenic factors from mitochondria to the cytosol. In this report, we investigated, by immunohistofluorescence, the in vivo distributio...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2007.00660.x

    authors: Zuliani T,Obriot H,Tual M,Lachman-Weber N,Dumas M,Formstecher P,Polakowska R,Ratinaud MH

    更新日期:2008-02-01 00:00:00

  • A single dose of interleukin-31 (IL-31) causes continuous itch-associated scratching behaviour in mice.

    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

    authors: Arai I,Tsuji M,Takeda H,Akiyama N,Saito S

    更新日期:2013-10-01 00:00:00

  • Neurophysiological and neurochemical basis of modern pruritus treatment.

    abstract::Chronic pruritus of any origin is a frequent discomfort in daily medical practice, and its therapy is challenging. Frequently, the underlying origin may not be identified and symptomatic therapy is necessary. Conventional treatment modalities such as antihistamines often lack efficacy, and hence new therapeutic strate...

    journal_title:Experimental dermatology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-0625.2007.00664.x

    authors: Ständer S,Weisshaar E,Luger TA

    更新日期:2008-03-01 00:00:00

  • Molecular genetic analysis of 16 XP-C patients from Germany: environmental factors predominately contribute to phenotype variations.

    abstract::Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise one-third of all XP patients. Only four major reports compiled larger groups of XP-C patients from southern Europe (12 pts), North America (16 pts) and Africa (14 and 56 pts) as well as their genetic background (46 XPC mutations). We ide...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12052

    authors: Schäfer A,Hofmann L,Gratchev A,Laspe P,Schubert S,Schürer A,Ohlenbusch A,Tzvetkov M,Hallermann C,Reichrath J,Schön MP,Emmert S

    更新日期:2013-01-01 00:00:00

  • Texture analysis of second-harmonic-generation images for quantitative analysis of reticular dermal collagen fibre in vivo in human facial cheek skin.

    abstract::Second-harmonic-generation (SHG) microscopy is a powerful tool for in vivo visualisation of collagen fibres in human skin because of its specific collagen selectivity without the need for staining, non-invasiveness and high-resolution three-dimensional imaging. Although texture analysis of SHG images is a promising me...

    journal_title:Experimental dermatology

    pub_type: 临床试验,杂志文章

    doi:10.1111/exd.13560

    authors: Ogura Y,Tanaka Y,Hase E,Yamashita T,Yasui T

    更新日期:2019-08-01 00:00:00

  • Combining confocal Raman microscopy and freeze-drying for quantification of substance penetration into human skin.

    abstract::In the area of dermatological research, the knowledge of rate and extent of substance penetration into the human skin is essential not only for evaluation of therapeutics, but also for risk assessment of chemicals and cosmetic ingredients. Recently, confocal Raman microscopy emerged as a novel analytical technique for...

    journal_title:Experimental dermatology

    pub_type: 信件

    doi:10.1111/exd.12542

    authors: Franzen L,Anderski J,Planz V,Kostka KH,Windbergs M

    更新日期:2014-12-01 00:00:00