Inhibition of keratin 17 expression with antisense and RNAi strategies: exploring novel therapy for psoriasis.


:Psoriasis is now considered to be a chronic, immune-mediated and inflammatory skin disease. As the precise cause of psoriasis remains unknown, its treatment is challenging for dermatologists. Keratin 17 (K17), an intermediate filament protein, is highly expressed in psoriatic lesions, while not normally expressed in healthy epidermis. Studies have suggested that K17 plays a role in the pathogenesis of psoriasis. However, no study has been performed to determine the potential application of K17 down-regulation as a treatment option for psoriatic lesions. We hypothesized that anti-K17 interference may suppress the development and progression of psoriasis and potentially serve as a novel strategy for the treatment of psoriasis. Therefore, we down-regulated and silenced K17 gene expression in keratinocytes (KCs) using antisense and RNA interference (RNAi) techniques. We found that K17-specific antisense oligonucleotides (ASODN) or siRNAs inhibited proliferation and induced apoptosis in KCs as well as down-regulated K17 expression at both mRNA and protein levels. For our in vivo study, we constructed the SCID-hu xenogeneic transplantation psoriasis mouse model by grafting psoriatic lesions onto SCID mice and topically applied K17-specific ASODN and liposome-encapsulated siRNA to the grafts. We observed morphological and histological improvement in the treated psoriatic grafts. As a result, K17 mRNA and protein expression was significantly decreased in the grafts of the mouse model. Taken together, we conclude that anti-K17 therapy is an effective treatment option for psoriasis, and the K17 molecule, as a new target, may hold tremendous potential for the treatment of psoriasis in the future.


Exp Dermatol


Experimental dermatology


Chang T,Sun L,Wang Y,Wang D,Li W,Li C,Gao T,Liu Y,Wang G




Has Abstract


2011-07-01 00:00:00












  • A high frequency of allergen-specific CD8+ Tc1 cells is associated with the murine immune response to the contact sensitizer trinitrophenyl.

    abstract::Chemical haptens induce a variety of allergic immune reactions by induction of hapten-specific T cells. Contact sensitizers such as the hapten trinitrochlorobenzene (TNCB) elicit an allergic response, which is confined to the area of antigen exposure. Despite this localized allergic response, we show here that the tri...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Martin S,Delattre V,Leicht C,Weltzien HU,Simon JC

    更新日期:2003-02-01 00:00:00

  • Long non-coding RNA TSIX is upregulated in scleroderma dermal fibroblasts and controls collagen mRNA stabilization.

    abstract::Long non-coding RNAs (lncRNAs) are thought to have various functions other than RNA silencing. We tried to evaluate the expression of lncRNAs in patients with systemic sclerosis (SSc) and determined whether lncRNAs controls collagen expression in dermal fibroblasts. lncRNA expression was determined by real-time PCR an...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Wang Z,Jinnin M,Nakamura K,Harada M,Kudo H,Nakayama W,Inoue K,Nakashima T,Honda N,Fukushima S,Ihn H

    更新日期:2016-02-01 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


    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

  • Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of l-plastin in atopic dermatitis.

    abstract::Infiltration of eosinophils in atopic dermatitis (AD), which contains inflammatory molecules and cytokines, recruits more inflammatory cells and causes further skin damage. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that induces the proinflammatory Th2 immune response and plays an important role in ...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Noh JY,Shin JU,Park CO,Lee N,Jin S,Kim SH,Kim JH,Min A,Shin MH,Lee KH

    更新日期:2016-11-01 00:00:00

  • How to define chronic pruritus: Symptom or disease?

    abstract::Chronic pruritus (CP) is defined by itching lasting 6 weeks or more and is known to be both a highly prevalent and burdensome symptom of many pruritogenic diseases. Its status as a symptom has many implications mainly that the symptom should evolve and subside with the disease. However, according to the clinical exper...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Ständer S

    更新日期:2019-12-01 00:00:00

  • Balance of Treg versus T-effector cells during systemic treatment with adalimumab and topical treatment with calcipotriol-betamethasone dipropionate ointment.

    abstract::Diminished suppressive capacity of regulatory T cells (Treg) has been demonstrated in blood and in lesional skin of psoriatic patients. Treatment with anti-TNFα restored the number and function of circulating Treg in psoriasis. We aimed to study Treg in the skin of psoriatic patients undergoing topical treatment with ...

    journal_title:Experimental dermatology

    pub_type: 信件


    authors: Keijsers RR,Joosten I,Hendriks AG,Koenen HJ,van Erp PE,van de Kerkhof PC

    更新日期:2015-01-01 00:00:00

  • Local rh-VEGF administration enhances skin flap survival more than other types of rh-VEGF administration: a clinical, morphological and immunohistochemical study.

    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


    authors: Scalise A,Tucci MG,Lucarini G,Giantomassi F,Orlando F,Pierangeli M,Pugnaloni A,Bertani A,Ricotti G,Biagini G

    更新日期:2004-11-01 00:00:00

  • Sirtuin-6 deficiency exacerbates diabetes-induced impairment of wound healing.

    abstract::Delayed wound healing is one of the major complications in diabetes and is characterized by chronic proinflammatory response, and abnormalities in angiogenesis and collagen deposition. Sirtuin family proteins regulate numerous pathophysiological processes, including those involved in promotion of longevity, DNA repair...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Thandavarayan RA,Garikipati VN,Joladarashi D,Suresh Babu S,Jeyabal P,Verma SK,Mackie AR,Khan M,Arumugam S,Watanabe K,Kishore R,Krishnamurthy P

    更新日期:2015-10-01 00:00:00

  • Increased serum HMGB1 levels in patients with Henoch-Schönlein purpura.

    abstract::High-mobility group box-1 (HMGB1) has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in Henoch-Schönlein purpura (HSP) is still unclear. Herein, we investigated the role of HMGB1 in patients with HSP and the pro-infla...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Chen T,Guo ZP,Wang WJ,Qin S,Cao N,Li MM

    更新日期:2014-06-01 00:00:00

  • Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation.

    abstract::Sangre de drago (SD) is a viscous bright red resin collected from Croton lechleri trees that grow in the South American jungle. This sap is used extensively in the native pharmacopoeia to treat skin disorders. Its effectiveness as an inhibitor of neurogenic inflammation has been recently demonstrated. To understand th...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Pereira U,Garcia-Le Gal C,Le Gal G,Boulais N,Lebonvallet N,Dorange G,Lefeuvre L,Gougerot A,Misery L

    更新日期:2010-09-01 00:00:00

  • Induction of matrix metalloproteinase-1 by small interfering RNA targeting connective tissue growth factor in dermal fibroblasts from patients with systemic sclerosis.

    abstract::We aimed to evaluate the effect of small interfering RNA (siRNA) targeting CTGF on extracellular matrices (ECMs) metabolism in normal and SSc fibroblasts. Normal and SSc fibroblasts were transfected with CTGF-specific siRNAs to silence CTGF synthesis. After silencing CTGF, production of type I collagen and matrix meta...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Ishibuchi H,Abe M,Yokoyama Y,Ishikawa O

    更新日期:2010-08-01 00:00:00

  • Itch-associated scratching contributes to the development of dermatitis and hyperimmunoglobulinaemia E in NC/Nga mice.

    abstract::Atopic dermatitis (AD) is related to immunoglobulin E (IgE) production, and a type-1 and type-2 helper T cell (Th1/Th2) imbalance has been hypothesized as the aetiology. While itching and scratching are important factors in the development of dermatitis, the mechanisms underlying these phenomena are poorly understood....

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Hashimoto Y,Takaoka A,Sugimoto M,Honma Y,Sakurai T,Futaki N,Arai I

    更新日期:2011-10-01 00:00:00

  • Rapid, high-quality and epidermal-specific isolation of RNA from human skin.

    abstract::As global transcriptome analyses with a growing demand on layer-specific applications are widely used in cutaneous biology, we investigated the effect of established and optimized dermo-epidermal separation methods on the quality of RNA. We compared enzymatic separation with dispase, chemical separation with 1 M sodiu...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Trost A,Bauer JW,Lanschützer C,Laimer M,Emberger M,Hintner H,Onder K

    更新日期:2007-03-01 00:00:00

  • Decorin-expressing adenovirus decreases collagen synthesis and upregulates MMP expression in keloid fibroblasts and keloid spheroids.

    abstract::Decorin is a natural transforming growth factor-β1 (TGF-β1) antagonist. Reduced decorin synthesis is associated with dermal scarring, and increased decorin expression appears to reduce scar tissue formation. To investigate the therapeutic potential of decorin for keloids, human dermal fibroblasts (HDFs) and keloid-der...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Lee WJ,Ahn HM,Roh H,Na Y,Choi IK,Lee JH,Kim YO,Lew DH,Yun CO

    更新日期:2015-08-01 00:00:00

  • In vitro and in vivo analysis of pro- and anti-inflammatory effects of weak and strong contact allergens.

    abstract::Inflammation is a crucial step in the development of allergic contact dermatitis. The primary contact with chemical allergens, called sensitization, and the secondary contact, called elicitation, result in an inflammatory response in the skin. The ability of contact allergens to induce allergic contact dermatitis corr...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Lass C,Merfort I,Martin SF

    更新日期:2010-11-01 00:00:00

  • Messenger RNAs for the multifunctional cytokines interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor-alpha are present in adnexal tissues and in dermis of normal human skin.

    abstract::Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are 3 cytokines that play a key rôle in cutaneous homeostasis and in the immunopathogenesis of a number of dermatologic diseases. Most studies have focused on their production by keratinocytes and Langerhans ce...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Boehm KD,Yun JK,Strohl KP,Elmets CA

    更新日期:1995-12-01 00:00:00

  • Depth profiling of Stratum corneum hydration in vivo: a comparison between conductance and confocal Raman spectroscopic measurements.

    abstract::The high-frequency electrical conductance of tape-stripped human skin in vivo can be used to evaluate the hydration profile of Stratum corneum (SC). Tape-stripping provides access to the underlying SC layers, and the conductance of these layers (as measured by the Skicon instrument) correlates well with their water co...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Boncheva M,de Sterke J,Caspers PJ,Puppels GJ

    更新日期:2009-10-01 00:00:00

  • Pathogenesis of mechanobullous disorders.

    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


    authors: Bruckner-Tuderman L

    更新日期:1992-10-01 00:00:00

  • Tiled array-based sequencing identifies enrichment of loss-of-function variants in the highly homologous filaggrin gene in African-American children with severe atopic dermatitis.

    abstract::Filaggrin (FLG) loss-of-function (LOF) variants are a major risk factor for the common inflammatory skin disease, atopic dermatitis (AD) and are often population-specific. African-American (AA) children are disproportionately affected with AD, often later developing asthma and/or allergic rhinitis and comprise an atop...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Mathyer ME,Quiggle AM,Wong XFCC,Denil SLIJ,Kumar MG,Ciliberto HM,Bayliss SJ,Common JE,de Guzman Strong C

    更新日期:2018-09-01 00:00:00

  • Dermal mast cells affect the development of sunlight-induced skin tumours.

    abstract::Ultraviolet (UV) radiation contained in sunlight is considered a major risk in the induction of skin cancer. While mast cells are best known for their role in allergic responses, they have also been shown to play a crucial role in suppressing the anti-tumour immune response following UV exposure. Evidence is now emerg...

    journal_title:Experimental dermatology

    pub_type: 杂志文章,评审


    authors: Sarchio SN,Kok LF,O'Sullivan C,Halliday GM,Byrne SN

    更新日期:2012-04-01 00:00:00

  • Genetic polymorphisms altering microRNA activity in psoriasis--a key to solve the puzzle of missing heritability?

    abstract::Psoriasis is a chronic immune-mediated skin disease in which the balance in the interplay of immune cells and keratinocytes is disturbed. MicroRNAs (miRNAs) are endogenous small regulatory RNAs that stabilize cellular phenotypes and fine-tune signal transduction feedback loops through the regulation of gene networks. ...

    journal_title:Experimental dermatology

    pub_type: 杂志文章,评审


    authors: Pivarcsi A,Ståhle M,Sonkoly E

    更新日期:2014-09-01 00:00:00

  • A colorimetric bead-binding assay for detection of intermolecular interactions.

    abstract::We have developed a new technique that rapidly and reproducibly allows direct visualization of molecular interactions, including receptor-ligand binding. The technique can be easily applied to examine binding between proteins and glycoproteins, or proteins and glycolipids, including gangliosides. In this novel bead-bi...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Irvine AD,Sun P,Kos L,Wang XQ,Paller AS

    更新日期:2002-10-01 00:00:00

  • Involvement of changes in stratum corneum keratin in wrinkle formation by chronic ultraviolet irradiation in hairless mice.

    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


    authors: Kambayashi H,Odake Y,Takada K,Funasaka Y,Ichihashi M

    更新日期:2003-01-01 00:00:00

  • Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris.

    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


    authors: Hariton WVJ,Galichet A,Vanden Berghe T,Overmiller AM,Mahoney MG,Declercq W,Müller EJ

    更新日期:2017-12-01 00:00:00

  • Suppression of melanogenesis by induction of endogenous intracellular metallothionein in human melanocytes.

    abstract::Nitric oxide (NO) is a potent intercellular mediator of melanogenesis, whereas metallothionein (MT) is an inducible intracellular antioxidant that has been reported to scavenge NO. We investigated the existence and induction of MT in melanocytes, and its inhibitory effect on NO-induced melanogenesis. The expression of...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Sasaki M,Kizawa K,Igarashi S,Horikoshi T,Uchiwa H,Miyachi Y

    更新日期:2004-08-01 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


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

    更新日期:2013-02-01 00:00:00

  • Influence of interleukin-1alpha on androgen receptor expression and cytokine secretion by cultured human dermal papilla cells.

    abstract::Dermal papilla cells (DPC) control the growth character of the hair follicle through their elaboration of mitogenic factors and extracellular matrix components. Further, the dermal papilla is a primary site of androgen action in the hair follicle. Interleukin-1alpha (IL-1alpha) is prominent in skin wounding and inflam...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Boivin WA,Jiang H,Utting OB,Hunt DW

    更新日期:2006-10-01 00:00:00

  • Molecular genetics of pseudoxanthoma elasticum.

    abstract::Pseudoxanthoma elasticum (PXE), a systemic heritable connective tissue disorder, is characterized by progressive calcification of elastic structures in the skin, the eyes and the cardiovascular system, with considerable intra- and interfamilial phenotypic variability. Recently, underlying genetic defects have been ide...

    journal_title:Experimental dermatology

    pub_type: 杂志文章,评审


    authors: Ringpfeil F,Pulkkinen L,Uitto J

    更新日期:2001-08-01 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


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

    更新日期:2013-10-01 00:00:00

  • Probing skin physiology through the volatile footprint: Discriminating volatile emissions before and after acute barrier disruption.

    abstract::Volatile organic compounds emitted by human skin were sampled before and after acute barrier disruption of the volar forearm to investigate the significance of this approach to skin physiology research. A small wearable housing integrating a solid-phase micro-extraction fibre permitting rapid enclosed headspace sampli...

    journal_title:Experimental dermatology

    pub_type: 杂志文章


    authors: Duffy E,Jacobs MR,Kirby B,Morrin A

    更新日期:2017-10-01 00:00:00