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https://www.readbyqxmd.com/read/28899688/keratins-regulate-the-adhesive-properties-of-desmosomal-cadherins-through-signaling
#1
Franziska Vielmuth, Marie-Therès Wanuske, Mariya Y Radeva, Matthias Hiermaier, Daniela Kugelmann, Elias Walter, Fanny Buechau, Thomas M Magin, Jens Waschke, Volker Spindler
Tightly controlled intercellular adhesion is crucial for integrity and function of the epidermis. The keratin filament cytoskeleton anchors desmosomes, supramolecular complexes required for strong intercellular adhesion. We here tested whether keratin filaments control cell adhesion by regulating the adhesive properties of desmosomal cadherins such as desmoglein (Dsg) 3. Atomic force microscopy (AFM) and FRAP experiments revealed reduced Dsg3 adhesive forces and membrane stability in murine keratinocytes lacking all keratin filaments...
September 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28899010/modelling-apoe-%C3%A9-3-4-allele-associated-sporadic-alzheimer-s-disease-in-an-induced-neuron
#2
Hongwon Kim, Junsang Yoo, Jaein Shin, Yujung Chang, Junghyun Jung, Dong-Gyu Jo, Janghwan Kim, Wonhee Jang, Christopher J Lengner, Byung-Soo Kim, Jongpil Kim
The recent generation of induced neurons by direct lineage conversion holds promise for in vitro modelling of sporadic Alzheimer's disease. Here, we report the generation of induced neuron-based model of sporadic Alzheimer's disease in mice and humans, and used this system to explore the pathogenic mechanisms resulting from the sporadic Alzheimer's disease risk factor apolipoprotein E (APOE) ɛ3/4 allele. We show that mouse and human induced neurons overexpressing mutant amyloid precursor protein in the background of APOE ɛ3/4 allele exhibit altered amyloid precursor protein (APP) processing, abnormally increased production of amyloid-β42 and hyperphosphorylation of tau...
August 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28888784/malignant-ascites-determine-the-transmesothelial-invasion-of-ovarian-cancer-cells
#3
Justyna Mikuła-Pietrasik, Paweł Uruski, Sebastian Szubert, Dariusz Szpurek, Stefan Sajdak, Andrzej Tykarski, Krzysztof Książek
The exact role of malignant ascites in the development of intraperitoneal ovarian cancer metastases remains unclear. In this report we sought to establish if ascites can determine the efficiency of transmesothelial invasion of ovarian cancer cells, and, if so, whether the fluid generated by highly aggressive serous and undifferentiated tumors will promote the invasion more effectively than ascites from less aggressive clear cell and endometrioid cancers. The study showed that the invasion of ovarian cancer cells (SKOV-3 and primary cancer cells) across monolayered peritoneal mesothelial cells was elevated upon mesothelial cell exposure to fluid produced by serous and undifferentiated cancers, as compared with cells subjected to ascites from clear cell and endometrioid tumors...
September 6, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28868524/divergent-specificity-development-of-igg1-and-igg4-autoantibodies-in-endemic-pemphigus-foliaceus-fogo-selvagem
#4
Mike Maldonado, Luis A Diaz, Phillip Prisayanh, Jinsheng Yang, Bahjat F Qaqish, Valeria Aoki, Gunter Hans-Filho, Evandro A Rivitti, Donna A Culton, Ye Qian
We have shown that although the IgG response in fogo selvagem (FS) is mainly restricted to desmoglein (Dsg) 1, other keratinocyte cadherins are also targeted by FS patients and healthy control subjects living in the endemic region of Limão Verde, Brazil (endemic controls). Evaluating nonpathogenic IgG1 and pathogenic IgG4 subclass responses to desmosomal proteins may reveal important differences between pathogenic and nonpathogenic responses, and how these differences relate to the pathogenic IgG4 response and resultant FS...
August 1, 2017: Immunohorizons
https://www.readbyqxmd.com/read/28864500/kr%C3%A3-ppel-like-factor-5-is-essential-for-maintenance-of-barrier-function-in-mouse-colon
#5
Yang Liu, Martyn Chidgey, Vincent W Yang, Agnieszka B Bialkowska
Krüppel-like factor 5 (KLF5) is a member of the zinc finger family of transcription factors that regulates homeostasis of the intestinal epithelium. Previous studies suggested an indispensable role of KLF5 in maintaining intestinal barrier function. In the current study, we investigated the mechanisms by which KLF5 regulates colonic barrier function in vivo and in vitro. We used an inducible and a constitutive intestine-specific Klf5 knockout mouse model (Villin-CreER(T2);Klf5(fl/fl) designated as Klf5(ΔIND) and Villin-Cre;Klf5(fl/fl) as Klf5(ΔIS) ), and studied an inducible KLF5 knockdown in Caco-2 BBe cells using a lentiviral Tet-on system (Caco-2 BBe KLF5ΔIND)...
September 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28855908/cytokine-and-chemokines-alterations-in-the-endemic-form-of-pemphigus-foliaceus-fogo-selvagem
#6
Rodolfo Pessato Timóteo, Marcos Vinicius Silva, Djalma Alexandre Alves da Silva, Jonatas Da Silva Catarino, Fernando Henrique Canhoto Alves, Virmondes Rodrigues Júnior, Ana Maria Roselino, Helioswilton Sales-Campos, Carlo José Freire Oliveira
INTRODUCTION: The endemic form (fogo selvagem-FS) of pemphigus foliaceus is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-1. Despite the array of findings, the role of chemokines and cytokines that dictate the immune response and disease outcome is still poorly investigated. MATERIALS AND METHODS: Serum from 64 patients diagnosed with FS was used to draw and establish the levels of these molecules on this disease and establish the levels of these molecules with the severity of FS, and influence of treatment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28833273/reinforcement-of-barrier-function-and-scalp-homeostasis-by-senkyunolide-a-to-fight-against-dandruff
#7
Philippe Mondon, Caroline Ringenbach, Emmanuel Doridot, Viviane Genet, Pascaline Criton
OBJECTIVE: Senkyunolide-A (SENKY) can be isolated from Apium graveolens seed oil obtained using supercritical CO2 extraction. SENKY and its parent compounds, the N-butyl phthalides, have been demonstrated to protect cells from CO poisoning, to prevent diabetes mellitus and to decrease cancer cell proliferation. This study was undertaken to evaluate in vitro and in vivo the effect of SENKY on epidermal function improvement, Malassezia effect control, scalp soothing and dandruff reduction via skin protection related pathways...
August 18, 2017: International Journal of Cosmetic Science
https://www.readbyqxmd.com/read/28821283/gene-expression-profiling-of-idiopathic-interstitial-pneumonias-iips-identification-of-potential-diagnostic-markers-and-therapeutic-targets
#8
Yasushi Horimasu, Nobuhisa Ishikawa, Masaya Taniwaki, Kakuhiro Yamaguchi, Kosuke Hamai, Hiroshi Iwamoto, Shinichiro Ohshimo, Hironobu Hamada, Noboru Hattori, Morihito Okada, Koji Arihiro, Yuji Ohtsuki, Nobuoki Kohno
BACKGROUND: Chronic fibrosing idiopathic interstitial pneumonia (IIP) is characterized by alveolar epithelial damage, activation of fibroblast proliferation, and loss of normal pulmonary architecture and function. This study aims to investigate the genetic backgrounds of IIP through gene expression profiling and pathway analysis, and to identify potential biomarkers that can aid in diagnosis and serve as novel therapeutic targets. METHODS: RNA extracted from lung specimens of 12 patients with chronic fibrosing IIP was profiled using Illumina Human WG-6 v3 BeadChips, and Ingenuity Pathway Analysis was performed to identify altered functional and canonical signaling pathways...
August 18, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28818065/case-reports-of-two-pedigrees-with-recessive-arrhythmogenic-right-ventricular-cardiomyopathy-associated-with-homozygous-thr335ala-variant-in-dsg2
#9
Sami Qadri, Olli Anttonen, Juho Viikilä, Eija H Seppälä, Samuel Myllykangas, Tero-Pekka Alastalo, Miia Holmström, Tiina Heliö, Juha W Koskenvuo
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease, involving changes in ventricular myocardial tissue and leading to fatal arrhythmias. Mutations in desmosomal genes are thought to be the main cause of ARVC. However, the exact molecular genetic etiology of the disease still remains largely inconclusive, and this along with large variabilities in clinical manifestations complicate clinical diagnostics. CASE PRESENTATION: We report two families (n = 20) in which a desmoglein-2 (DSG2) missense variant c...
August 17, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28803268/proteomic-profiling-of-the-dystrophin-complex-and-membrane-fraction-from-dystrophic-mdx-muscle-reveals-decreases-in-the-cytolinker-desmoglein-and-increases-in-the-extracellular-matrix-stabilizers-biglycan-and-fibronectin
#10
Sandra Murphy, Heinrich Brinkmeier, Mirjam Krautwald, Michael Henry, Paula Meleady, Kay Ohlendieck
The almost complete loss of the membrane cytoskeletal protein dystrophin and concomitant drastic reduction in dystrophin-associated glycoproteins are the underlying mechanisms of the highly progressive neuromuscular disorder Duchenne muscular dystrophy. In order to identify new potential binding partners of dystrophin or proteins in close proximity to the sarcolemmal dystrophin complex, proteomic profiling of the isolated dystrophin-glycoprotein complex was carried out. Subcellular membrane fractionation and detergent solubilisation, in combination with ion exchange, lectin chromatography and density gradient ultracentrifugation, was performed to isolate a dystrophin complex-enriched fraction...
August 12, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28791421/erratum-to-autoantibodies-to-desmogleins-1-and-3-in-patients-with-lichen-planus
#11
Vahide Lajevardi, Zahra Halaji, Forugh Ghaedi, Nazi Saljoughi
No abstract text is available yet for this article.
August 8, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28764973/disturbed-desmoglein-2-in-the-intercalated-disc-of-pediatric-patients-with-dilated-cardiomyopathy
#12
Elise L Kessler, Peter Gj Nikkels, Toon Ab van Veen
Dilated cardiomyopathy (DCM) leads to disturbed contraction and force transduction, and is associated with substantial mortality in all age groups. Involvement of a disrupted composition of the intercalated disc (ID) has been reported. However, in children, little is established about such subcellular changes during disease, because of the pathological mix-up with the ongoing cardiac maturation. This leaves maladaptive remodeling often undetected. We aimed at illustrating subcellular alterations in children diagnosed with DCM compared to age-matched controls, focusing on ID proteins known to be crucially stable under healthy conditions and destabilized during cardiac injury in adults...
July 29, 2017: Human Pathology
https://www.readbyqxmd.com/read/28740698/robotic-trans-subxiphoid-extended-thymectomy-in-a-patient-with-thymoma-associated-pemphigus
#13
Yu Zheng, Yi-Zhou Cai, Han-Lu Zhang, Zi-Hao Wang, Yun Wang
We herein firstly reported that a patient with thymoma-associated pemphigus (TAP) underwent a robotic-assisted trans-subxiphoid thoracoscopic extended thymectomy and then achieved stable resolution. The patient, a 47-year-old male, was first admitted to our hospital owing to stomatitis and bullae of the trunk after four months' prednisone treatment. On admission, chest computed tomography (CT) revealed an anterior-mediastinal mass and it was initially diagnosed as a thymoma. He was positive for anti-BP (bullous pemphigoid)-180 antibody and anti-desmoglein 3 antibody...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28740231/desmoglein-2-regulates-the-intestinal-epithelial-barrier-via-p38-mitogen-activated-protein-kinase
#14
Hanna Ungewiß, Franziska Vielmuth, Shintaro T Suzuki, Andreas Maiser, Hartmann Harz, Heinrich Leonhardt, Daniela Kugelmann, Nicolas Schlegel, Jens Waschke
Intestinal epithelial barrier properties are maintained by a junctional complex consisting of tight junctions (TJ), adherens junctions (AJ) and desmosomes. Desmoglein 2 (Dsg2), an adhesion molecule of desmosomes and the only Dsg isoform expressed in enterocytes, is required for epithelial barrier properties and may contribute to barrier defects in Crohn's disease. Here, we identified extradesmosomal Dsg2 on the surface of polarized enterocytes by Triton extraction, confocal microscopy, SIM and STED. Atomic force microscopy (AFM) revealed Dsg2-specific binding events along the cell border on the surface of enterocytes with a mean unbinding force of around 30pN...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28674915/autoantibodies-to-desmogleins-1-and-3-in-patients-with-lichen-planus
#15
Lajevardi Vahide, Halaji Zahra, Ghaedi Forugh, Saljoughi Nazi
There is controversy about the role of autoantibodies against desmoglein 1 and 3 (Dsg1 and 3) in the pathogenesis of lichen planus (LP); the authors planned this study to determine the presence of circulating levels of these antibodies in patients with different types of oral LP and to compare that with cutaneous LP and healthy controls. The enzyme-linked immunosorbent assay test was performed on serum samples of 24 cases of erosive oral LP, 29 cases of reticular oral LP, 30 cases of cutaneous LP and 30 healthy controls...
July 3, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28661086/selective-plasma-exchange-for-the-removal-of-pemphigus-autoantibodies-fibrinogen-and-factor-xiii-in-pemphigus-vulgaris
#16
Satoko Miyamoto, Atsushi Ohkubo, Hiroshi Seshima, Shigeto Komori, Motoki Yamamoto, Takuma Maeda, Ayako Itagaki, Hiroko Yamamoto, Kohei Nojima, Soichiro Iimori, Shotaro Naito, Naoki Kurashima, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida, Tomokazu Okado
Pemphigus vulgaris is a serious autoimmune skin disorder associated with desmoglein 1 and 3. Selective plasma exchange (SePE) for pemphigus vulgaris remains unknown. We investigated the removal characteristics of pemphigus autoantibodies, immunoglobulins, and fibrinogen in three cases. When the mean processed volume for SePE was 1.2 plasma volumes, the mean percent reduction was 50.7% for desmoglein 1, 48.9% for desmoglein 3, 50.3% for IgG, 29.8% for IgA, 1.9% for IgM, and 17.6% for fibrinogen. In one case, the percent reduction after four sessions of SePE within eight days was 87...
June 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28631092/rituximab-treatment-in-pemphigus-vulgaris-effect-on-circulating-tregs
#17
Bakr El-Zawahry, Dalia Bassiouny, Rehab Hegazy, Heba Gawdat, Suzan Shalaby, Mervat Khorshied, Marwah Adly Saleh
Rituximab (RTX) has been used successfully to treat refractory pemphigus. We aimed to assess the response of pemphigus vulgaris (PV) cases to RTX therapy and its effect on CD4(+)CD25(+) (T regulatory) cells level. Sixteen PV patients were included in this study, each received one cycle of two RTX infusions (1000 mg on days 1 and 15). Five PV patients served as controls. All cases were on prednisolone ± adjuvant therapy. Pemphigus disease area index (PDAI), autoimmune bullous skin intensity score (ABSIS), anti-desmoglein antibodies, CD4, CD8, CD20 and CD4(+)CD25(+) levels were assessed at baseline, 3, 6 and 12 months after therapy...
June 19, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28622444/paraneoplastic-pemphigus-in-two-pairs-of-brothers
#18
B Kranzelbinder, T Hashimoto, M Joch, W Salmhofer, H Reiter, J Bauer, E Aberer
A 65-year-old man (Patient 1A) presented with erosions on the face, upper trunk and the oral mucosa in 1995 (Table 1). He underwent prostatectomy for prostate cancer in 1990. PNP was proven by antibodies to IgG anti-epithelial cell surface (ECS), desmoglein (Dsg)1, and Dsg3. This article is protected by copyright. All rights reserved.
June 16, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28620161/different-signaling-patterns-contribute-to-loss-of-keratinocyte-cohesion-dependent-on-autoantibody-profile-in-pemphigus
#19
Elias Walter, Franziska Vielmuth, Lukas Rotkopf, Miklós Sárdy, Orsolya N Horváth, Matthias Goebeler, Enno Schmidt, Rüdiger Eming, Michael Hertl, Volker Spindler, Jens Waschke
Pemphigus is an autoimmune blistering skin disease caused primarily by autoantibodies against desmoglein (Dsg)1 and 3. Here, we characterized the mechanisms engaged by pemphigus IgG from patients with different clinical phenotypes and autoantibody profiles. All pemphigus vulgaris (PV) and pemphigus foliaceus (PF) IgG and AK23, a monoclonal mouse antibody against Dsg3, caused loss of cell cohesion, cytokeratin retraction and p38MAPK activation. Strong alterations in Dsg3 distribution were caused by mucosal (aDsg3 antibodies), mucocutaneous (aDsg1 + aDsg3) as well as atypical (aDsg3) PV-IgG...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28600798/inhibition-of-p38mapk-signaling-prevents-epidermal-blistering-and-alterations-of-desmosome-structure-induced-by-pemphigus-autoantibodies-in-human-epidermis
#20
D T Egu, E Walter, V Spindler, J Waschke
BACKGROUND: Pemphigus vulgaris (PV) is a skin blistering disease caused by autoantibodies targeting the desmosomal adhesion proteins desmoglein (Dsg) 3 and 1. The mechanisms underlying pemphigus skin blistering are not fully elucidated but p38MAPK activation is one of the signaling events necessary for full loss of cell cohesion. However, it is unclear whether ultrastructural hallmarks of desmosome morphology as observed in patients' lesions are mediated by p38MAPK signaling. OBJECTIVE: In this study, we tested the relevance of p38MAPK for blister formation and the ultrastructural changes induced by PV autoantibodies in human skin...
June 10, 2017: British Journal of Dermatology
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