Abstract：
BACKGROUND:Netherton syndrome (NS, MIM 256500) is a potential live threatening autosomal-recessive skin disorder clinically characterized by the trias of congenital erythroderma, hair shaft anomalies and atopic diathesis. It is caused by mutations in the gene SPINK5 resulting in a deficiency of its processed protein named lympho-epithelial Kazal-type related inhibitor (LEKTI). LEKTI controls the activity of several serine proteases in the skin that are involved in terminal differentiation. Loss of LEKTI results in protease hyperactivity, increased degradation of intercellular junctions, reduced stratum corneum adhesion and impaired skin barrier function. Today NS can only be treated symptomatically. OBJECTIVE:Does gene transfer offer a therapeutic option for NS in the future? METHODS:A recombinant adeno-associated virus type 2 vector was constructed containing the full length cDNA (rAAV2/C-SPINK5) of functional human LEKTI. Infectious virus particles were used for transfection of LEKTI-deficient-keratinocytes of NS patients in vitro. RESULTS:Gene transfer of SPINK5 in NS-keratinocytes led to a five-fold increase in mRNA expression of SPINK5 reaching almost 75% of normal value. The functionality of the expressed LEKTI was proven in a hydrolytic activity assay demonstrating that the activity of LEKTI after gene transfer increased closely to the level seen in keratinocytes of healthy individuals. CONCLUSION:The results provide first evidence that gene transfer of SPINK5 results in increased LEKTI activity in NS-keratinocytes, thus offering a rational to further pursue such a gene therapy approach for NS.
journal_name
J Dermatol Scijournal_title
Journal of dermatological scienceauthors
Roedl D,Oji V,Buters JT,Behrendt H,Braun-Falco Mdoi
10.1016/j.jdermsci.2010.12.004subject
Has Abstractpub_date
2011-03-01 00:00:00pages
194-8issue
3eissn
0923-1811issn
1873-569Xpii
S0923-1811(10)00393-2journal_volume
61pub_type
杂志文章abstract：BACKGROUND:The effects of hyaluronic acid (HA) injection on tissue collagen anabolism are suggested to be related to the induction of mechanical stress, causing biochemical changes in skin physiology. OBJECTIVES:To ascertain the association between dermal mechanics modulated by a hyaluronic acid-based filler effect an...
journal_title：Journal of dermatological science
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.jdermsci.2012.12.006
更新日期：2013-03-01 00:00:00
abstract：:Thiols are of great importance for the regulation of many cellular functions including metabolism, transport and cell protection. In this study the usefulness of L-cysteine methyl and octyl esters, of N,S-diacetyl-L-cysteine methyl ester and glutathione isopropyl ester as cellular cysteine and GSH delivery systems was...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/0923-1811(90)90008-2
更新日期：1990-01-01 00:00:00
abstract：BACKGROUND:We have focused on the DNA topoisomerase II genes of several pathogenic fungi, and developed polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) methods targeting this gene for identification of dermatophytes. OBJECTIVE:To assess the availability of the PCR-based identifi...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2003.10.007
更新日期：2004-02-01 00:00:00
abstract：BACKGROUND:Carbonylated proteins (CPs) are generated by the reaction of basic amino acid residues in proteins with aldehyde compounds produced during lipid peroxidation. CPs in the stratum corneum (SC) impact skin conditions such as skin moisture functions including water content and transepidermal water loss (TEWL). I...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2016.09.016
更新日期：2016-12-01 00:00:00
abstract：:Over the last decade, animal models of atopic dermatitis (AD) have received increasing attention. They include NC/Nga mice, a hapten-induced mouse model, and transgenic and knockout mouse models. Although the pathogenesis of skin inflammation elicited in these models and that in AD are not quite the same, it is pertin...
journal_title：Journal of dermatological science
pub_type： 杂志文章,评审
doi：10.1016/j.jdermsci.2004.02.013
更新日期：2004-10-01 00:00:00
abstract：BACKGROUND:Chemokines and their receptors are important elements for the selective attraction and activation of various subsets of leukocytes. Expression of CXCR3 ligands, such as monokine induced by IFN-gamma (Mig) leads to preferential Th1 recruitment, whereas CCR4 ligands, thymus and activation regulated chemokine (...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2004.01.001
更新日期：2004-05-01 00:00:00
abstract：:Kindler syndrome is an autosomal recessive genodermatosis characterized by acral blistering in neonates and diffuse, progressive poikiloderma in later life. Other clinical features include photosensitivity, premature skin ageing and severe periodontal disease. Two groups have recently shown that the molecular basis of...
journal_title：Journal of dermatological science
pub_type： 杂志文章,评审
doi：10.1016/j.jdermsci.2004.12.026
更新日期：2005-06-01 00:00:00
abstract：:Our previous study reported that advanced glycation end-products (AGE)-modified BSA produced active oxygen species, *O2-, H2O2, and *OH under UVA irradiation and enhanced the cytotoxicity of UVA light. We examined whether pentosidine in AGE-modified BSA was involved in one of the mechanisms generating the active oxyge...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/s0923-1811(01)00114-1
更新日期：2001-08-01 00:00:00
abstract：BACKGROUND:Human Apurinic/Apyrimidinic Endonuclease 1 (APE1/REF-1/HAP1) is a multifunction protein involved in the progression of cancer. But the role of APE1 in cutaneous squamous cell carcinoma (cSCC) is unclear. OBJECTIVE:This study is aimed to investigate the basic modulatory mechanism of APE1 in cSCC development ...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2020.08.012
更新日期：2020-10-01 00:00:00
abstract：:The initial lymphatics of the human skin do not possess a basal lamina, but a subendothelial fibrous network, of which we do not know the biochemical and immunohistological composition. We investigated the wall of blood vessels and initial lymphatics in normal human skin for the presence of fibronectin by immunoelectr...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/0923-1811(92)90060-o
更新日期：1992-09-01 00:00:00
abstract：:A cell line, designated ISOS-1, was established from a tumor formed by transplantation of a human angiosarcoma into mice with severe combined immunodeficiency (SCID). The cells showed endothelial properties, based on the uptake of Dil-Ac-LDL and binding of UEA-I/GSA-I lectins, but were negative for CD11b and Pan Cytok...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/s0923-1811(97)00032-7
更新日期：1998-01-01 00:00:00
abstract：BACKGROUND:UV radiation is the major environmental factor related to development of cutaneous melanoma. Besides sun exposure and the influence of latitude, some host characteristics such as skin phototype and hair and eye color are also risk factors for melanoma. Polymorphisms in DNA repair genes could be good candidat...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2011.06.003
更新日期：2011-10-01 00:00:00
abstract：:In order to investigate the mode of action of testosterone (T) on human hair follicles we studied the metabolism of T and localization of androgen receptors in outer root sheath cells (ORSC) and dermal papilla cells (DPC) from different body sites. T was principally metabolized to androstenedione (delta 4) even in bea...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/0923-1811(94)90040-x
更新日期：1994-07-01 00:00:00
abstract：BACKGROUND:The process of repair after skin injury is precisely regulated by a variety of mediators such as cytokines and chemokines. Recent reports demonstrated that cytoplasmic DNA-sensor cyclic GMP-AMP synthase (cGAS) activates the stimulator of interferon genes (STING) via production of cyclic GMP-AMP (cGAMP) and s...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2019.11.008
更新日期：2020-01-01 00:00:00
abstract：BACKGROUND:Rutin, due to its polyphenolic structure, has antioxidant properties and can be used as a cytoprotective compound against UV-induced effects on skin cells. OBJECTIVE:The aim of this study was to examine the effect of rutin on proteomic profile in human skin fibroblasts irradiated with UV dose that induces a...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2018.02.002
更新日期：2018-06-01 00:00:00
abstract：:Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency with angiokeratoma corporis diffusum (AKCD) is one of the lysosomal storage diseases. GalNAc(alpha))1-O-Ser/Thr (Tn) is theoretically deposited in lysosomes, but substances with attached galactose and neuraminic (sialic) acid (T and sialosyl Tn, respectively) are...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/s0923-1811(02)00005-1
更新日期：2002-05-01 00:00:00
abstract：:Injury to vessel walls, especially microvascular damage due to free radicals, has been a focus of interest concerning the pathogenesis of systemic sclerosis. Excess reactive oxygen species may induce antioxidant defenses. We therefore measured plasma superoxide dismutase (SOD) activity in patients with systemic sclero...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/0923-1811(95)00441-6
更新日期：1996-03-01 00:00:00
abstract：BACKGROUND:The tetracycline (Tet) responsive system is a valuable tool that is routinely used in a wide variety of mammalian cells for regulatable expression of gene products. However, technical difficulties such as harsh selection conditions and extensive screening processes to identify suitably responsive clones limi...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2007.09.003
更新日期：2008-01-01 00:00:00
abstract：BACKGROUND:Autophagy is a highly conserved cellular catabolic pathway for degradation and recycling of intracellular components in response to nutrient starvation or environmental stress. Endoplasmic reticulum (ER) homeostasis can be disturbed by physiological and pathological influences, resulting in accumulation of m...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2017.04.011
更新日期：2017-08-01 00:00:00
abstract：BACKGROUND:Transforming growth factor beta 1 (TGFβ) is known to be a regulator of autoimmunity. Loss of TGFβ leads to severe multi-organ autoimmunity in mice. In skin, role of TGFβ in suppressing autoimmunity is unclear. OBJECTIVE:Determine whether Keratinocyte (KC)-derived TGFβ is required for skin immune homeostasis...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2019.04.008
更新日期：2019-05-01 00:00:00
abstract：BACKGROUND:Various cutaneous manifestations have been observed in patients with COVID-19 infection. However, overall similarities in the clinical presentation of these dermatological manifestations have not yet been summarized. OBJECTIVE:This review aims to provide an overview of various cutaneous manifestations in pa...
journal_title：Journal of dermatological science
pub_type： 杂志文章,评审
doi：10.1016/j.jdermsci.2020.04.011
更新日期：2020-05-01 00:00:00
abstract：BACKGROUND:It is well known that cyclophosphamide (Cy) treatment before sensitization paradoxically enhances rather than suppresses contact hypersensitivity (CH) reactions. In fact, Cy-treated mice developed a significant (p < 0.05) increase of the CH reactions to 2,4,6-trinitro-1-chrolobenzene (TNCB) in comparison wit...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2005.02.002
更新日期：2005-08-01 00:00:00
abstract：BACKGROUND:The capacity of photosensitizing chemicals with ultraviolet A light (UVA) to induce apoptosis is one of the methods to assess their phototoxic and potentially photoallergic properties, since apoptotic cells may be easily presented by antigen-presenting cells. OBJECTIVES:We examined the photoaggravated abili...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2006.10.010
更新日期：2007-02-01 00:00:00
abstract：:Considerable evidence suggests that factor XIIIa, a blood coagulation factor, also functions in tissue repair, and specifically in the dynamic process of fibroplasia. On the other hand, the dynamic process of tissue expansion would require a loosening of the dermis, the opposite of fibroplasia. We examined the effects...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/0923-1811(91)90044-x
更新日期：1991-01-01 00:00:00
abstract：:In order to disclose the possible disturbance in regulation of p21ras function in neurofibromatosis type 1, we investigated the recovery from the quiescent to cycling states of the cell cycle in the skin fibroblasts of the patients. When cells cultured in serum-dependent medium are deprived of the serum, these go into...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/0923-1811(94)90082-5
更新日期：1994-04-01 00:00:00
abstract：:Hair follicles reconstitute themselves though the hair cycle, suggesting the presence of intrinsic stem cells. In contrast to the previous belief that stem cells reside in the bulbar region of hair follicles, stem cells were detected in the bulge area, a contiguous part of outer root sheath, that provides the insertio...
journal_title：Journal of dermatological science
pub_type： 杂志文章,评审
doi：10.1016/j.jdermsci.2006.12.002
更新日期：2007-05-01 00:00:00
abstract：BACKGROUND:Canine atopic dermatitis (cAD) is a common condition in dogs that may be a naturally occurring model for human atopic dermatitis (hAD). Despite this, comparative research is limited, particularly into the genetic background of cAD. OBJECTIVES:1. Measure candidate gene expression in cAD skin using quantitati...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2009.03.005
更新日期：2009-07-01 00:00:00
abstract：:We previously reported a simple and easy-to-use device, Scratch Monitor for evaluation of nocturnal scratching. In the present study, the effect of an antihistamine (azelastine hydrochloride) on atopic dermatitis was investigated using this device. In 40 patients with atopic dermatitis, nocturnal scratching was measur...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/s0923-1811(99)00048-1
更新日期：1999-12-01 00:00:00
abstract：:We examined the production of superantigenic exotoxins in 136 coagulase-negative staphylococci isolated from various skin lesions in humans using a reversed passive latex agglutination test (Denka Seiken). As a control we examined the same in 50 Staphylococcus aureus strains isolated from non-infective skin ulcers in ...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/s0923-1811(00)00122-5
更新日期：2000-11-01 00:00:00
abstract：BACKGROUND:Pruritus and discomfort are often present in patients with xerosis and atopic dermatitis. Several studies suggest an important role of diet in skin pathophysiology. OBJECTIVE:This study evaluated the effect of dietary fatty acids in the skin physiology via an itch-related animal model with and without suppl...
journal_title：Journal of dermatological science
pub_type： 杂志文章
doi：10.1016/j.jdermsci.2015.06.015
更新日期：2015-09-01 00:00:00
