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https://www.readbyqxmd.com/read/29352264/cell-autonomous-role-of-iaspp-deficiency-in-causing-cardiocutaneous-disorders
#1
Zinaida Dedeić, Gopinath Sutendra, Ying Hu, Kathryn Chung, Elizabeth A Slee, Michael J White, Felix Y Zhou, Robert D Goldin, David J P Ferguson, Debra McAndrew, Jurgen E Schneider, Xin Lu
Desmosome components are frequently mutated in cardiac and cutaneous disorders in animals and humans and enhanced inflammation is a common feature of these diseases. Previous studies showed that inhibitor of Apoptosis Stimulating p53 Protein (iASPP) regulates desmosome integrity at cell-cell junctions and transcription in the nucleus, and its deficiency causes cardiocutaneous disorder in mice, cattle, and humans. As iASPP is a ubiquitously expressed shuttling protein with multiple functions, a key question is whether the observed cardiocutaneous phenotypes are caused by loss of a cell autonomous role of iASPP in cardiomyocytes and keratinocytes specifically or by a loss of iASPP in other cell types such as immune cells...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29349851/clinical-and-molecular-implications-of-structural-changes-to-desmosomes-and-corneodesmosomes
#2
REVIEW
Akemi Ishida-Yamamoto, Satomi Igawa, Mari Kishibe, Masaru Honma
Desmosomes provide the main intercellular adhesive properties between epidermal keratinocytes. Their distribution becomes uneven in severe dermatitis, multiple allergies and metabolic wasting syndrome due to desmoglein 1 deficiency and the loss of intercellular adhesion or acantholysis. When keratinocytes differentiate from granular cells into cornified cells, desmosomes are transformed into corneodesmosomes and can provide stronger intercellular adhesion. Degradation of corneodesmosomes is a tightly regulated process involving a number of proteases and their inhibitors...
January 19, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29348685/overexpression-of-adhesion-molecules-and-barrier-molecules-is-associated-with-differential-infiltration-of-immune-cells-in-non-small-cell-lung-cancer
#3
Young Kwang Chae, Wooyoung M Choi, William H Bae, Jonathan Anker, Andrew A Davis, Sarita Agte, Wade T Iams, Marcelo Cruz, Maria Matsangou, Francis J Giles
Immunotherapy is emerging as a promising option for lung cancer treatment. Various endothelial adhesion molecules, such as integrin and selectin, as well as various cellular barrier molecules such as desmosome and tight junctions, regulate T-cell infiltration in the tumor microenvironment. However, little is known regarding how these molecules affect immune cells in patients with lung cancer. We demonstrated for the first time that overexpression of endothelial adhesion molecules and cellular barrier molecule genes was linked to differential infiltration of particular immune cells in non-small cell lung cancer...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29313220/pemphigus-a-comprehensive-review-on-pathogenesis-clinical-presentation-and-novel-therapeutic-approaches
#4
REVIEW
Robert Pollmann, Thomas Schmidt, Rüdiger Eming, Michael Hertl
Pemphigus is a group of rare, potentially devastating autoimmune diseases of the skin and mucous membranes with high morbidity and potentially lethal outcome. The major clinical variant, pemphigus vulgaris (PV) is caused by a loss of intercellular adhesion of epidermal keratinocytes which is induced by IgG autoantibodies against components of desmosomes. Specifically, IgG against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1), preferentially target their ectodomains which are presumably critical for the transinteraction and signalling function of these adhesion molecules...
January 8, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29307589/pathogenic-igg4-autoantibodies-from-endemic-pemphigus-foliaceus-recognize-a-desmoglein-1-conformational-epitope
#5
Flor Evangelista, Aleeza J Roth, Phillip Prisayanh, Brenda R Temple, Ning Li, Ye Qian, Donna A Culton, Zhi Liu, Oliver J Harrison, Julia Brasch, Barry Honig, Lawrence Shapiro, Luis A Diaz
Fogo Selvagem (FS), the endemic form of pemphigus foliaceus, is mediated by pathogenic IgG4 autoantibodies against the amino-terminal extracellular cadherin domain of the desmosomal cadherin desmoglein 1 (Dsg1). Here we define the detailed epitopes of these pathogenic antibodies. Proteolytic footprinting showed that IgG4 from 95% of FS donor sera (19/20) recognized a 16-residue peptide (A129LNSMGQDLERPLELR144) from the EC1 domain of Dsg1 that overlaps the binding site for an adhesive-partner desmosomal cadherin molecule...
January 4, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29291530/cellular-biomechanics-impairment-in-keratinocytes-is-associated-with-a-c-terminal-truncated-desmoplakin-an-atomic-force-microscopy-investigation
#6
Luca Puzzi, Daniele Borin, Valentina Martinelli, Luisa Mestroni, David P Kelsell, Orfeo Sbaizero
In a tissue continuously challenged by mechanical stresses, such as the skin or the heart, cells perceive information about their microenvironment through several adhesive protein complexes and activate cell-signaling events to maintain tissue cohesion. Consequently, alteration of cell adhesion components leads to aberrant assembly of the associated cytoplasmic scaffolding and signaling pathways, which may reflect changes to the tissue physiology and mechanical resistance. Desmoplakin is an essential component of the cell-cell junction, anchoring the desmosomal protein complex to the intermediate filaments (IFs)...
December 19, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/29288195/sequencing-of-linkage-region-on-chromosome-12p11-identifies-pkp2-as-a-candidate-gene-for-left-ventricular-mass-in-dominican-families
#7
Nicole D Dueker, Shengru Guo, Ashley Beecham, Liyong Wang, Susan H Blanton, Marco R Di Tullio, Tatjana Rundek, Ralph L Sacco
Increased left ventricular mass (LVM) is an intermediate phenotype for cardiovascular disease (CVD) and a predictor of stroke. Using families from the Dominican Republic, we have previously shown LVM to be heritable and found evidence for linkage to chromosome 12p11. Our current study aimed to further characterize the QTL by sequencing the 1 LOD unit down region in ten families from the Dominican Republic with evidence for linkage to LVM. Within this region, we tested 5,477 common variants (CVs; minor allele frequency [MAF] ≥5%) using the QTDT test...
December 29, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29273475/plectin-controls-biliary-tree-architecture-and-stability-in-cholestasis
#8
Marketa Jirouskova, Katerina Nepomucka, Gizem Oyman-Eyrilmez, Alzbeta Kalendova, Helena Havelkova, Lenka Sarnova, Karel Chalupsky, Bjoern Schuster, Oldrich Benada, Petra Miksatkova, Martin Kuchar, Ondrej Fabian, Radislav Sedlacek, Gerhard Wiche, Martin Gregor
BACKGROUND & AIMS: Plectin, a highly versatile cytolinker protein, controls intermediate filament (IF) cytoarchitecture and cellular stress response. In the present study, we investigate the role of plectin in the liver under basal conditions and in experimental cholestasis. METHODS: We generated liver-specific Plectin knockout (PleΔalb) mice and analyzed them using two cholestatic liver injury models: bile duct ligation (BDL) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding...
December 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29212005/desmoglein-3-order-and-dynamics-in-desmosomes-determined-by-fluorescence-polarization-microscopy
#9
Emily I Bartle, Tara M Urner, Siddharth S Raju, Alexa L Mattheyses
Desmosomes are macromolecular cell-cell junctions that provide adhesive strength in epithelial tissue. Desmosome function is inseparably linked to structure, and it is hypothesized that the arrangement, or order, of desmosomal cadherins in the intercellular space is critical for adhesive strength. However, due to desmosome size, molecular complexity, and dynamics, the role that order plays in adhesion is challenging to study. Herein, we present an excitation resolved fluorescence polarization microscopy approach to measure the spatiotemporal dynamics of order and disorder of the desmosomal cadherin desmoglein 3 (Dsg3) in living cells...
December 5, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29198699/activation-of-pkb-akt-and-p44-42-by-mechanical-stretch-utilizes-desmosomal-structures-and-the-keratin-filament
#10
Stefan Kippenberger, Johannes Kleemann, Markus Meissner, Katja Steinhorst, Jutta Müller, Christos C Zouboulis, Roland Kaufmann, Nadja Zöller
BACKGROUND: Mechanical stress is an ubiquitous challenge of human cells with fundamental impact on cell physiology. Previous studies have shown that stretching promotes signalling cascades involved in proliferation and tissue enlargement. OBJECTIVE: The present study is dedicated to learn more about cellular structures contributing to perception and signal transmission of cell stretch. In particular, we hypothesized that desmosmal contacts and the adjacent keratin filament build an intercellular matrix providing information about the mechanical load...
November 30, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29179007/electron-microscopy-observations-on-testis-and-spermatozoa-of-leptodactylus-chaquensis-anura-leptodactylidae
#11
Lucrecia Iruzubieta Villagra, Inés Ramos, Susana Cisint, Claudia A Crespo, Silvia N Fernández
Scanning and transmission electron microscopy were used to investigate the fine structure of the testis and spermatozoa of toad Leptodactylus chaquensis. Our observations indicate that germinal compartment contains Sertoli (SC) and germ cells. The tight junctions and desmosomes among SC indicate the existence of an hematotesticular barrier in charge of maintaining the differences in the composition of the germinal and interstitial compartments. During spermatogenesis, SC acts as a structural support for germ cells...
November 21, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/29178656/unique-genetic-background-and-outcome-of-non-caucasian-japanese-probands-with-arrhythmogenic-right-ventricular-dysplasia-cardiomyopathy
#12
Yuko Wada, Seiko Ohno, Takeshi Aiba, Minoru Horie
BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy mainly caused by desmosomal gene mutation. More than half of Caucasian probands have desmosomal mutations, which lead to earlier onset of ventricular arrhythmias. Among non-Caucasians, the genetic background of ARVD/C probands and its prognostic impact remain unclear. METHODS AND RESULTS: We genotyped 99 unrelated Japanese ARVD/C probands for plakophilin 2 (PKP2), desmoglein 2 (DSG2), desmoplakin (DSP), and desmocollin 2 (DSC2) between 2005 and 2014...
November 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29159879/new-insights-into-pemphigoid-diseases
#13
Frank Antonicelli, Ralf J Ludwig
Pemphigus and pemphigoid diseases are organ-specific autoimmune blistering diseases (AIBD), characterized and caused by autoantibodies to structural components of the skin (1). The autoantigens targeted in pemphigus are desmoglein 1 and 3, two proteins of the desmosomal structure, while the autoantigens in pemphigoid diseases (PD) are components of the basal membrane. For example, bullous pemphigoid (BP), the most frequent PD is characterized by autoantibodies against type XVII collagen (COL17, BP180) and BP230, and epidermolysis bullosa acquisita (EBA) is caused by autoantibodies against type VII collagen (COL7)...
November 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29146182/plakophilin3-increases-desmosome-assembly-size-and-stability-by-increasing-expression-of-desmocollin2
#14
Mansa Gurjar, Kumarkrishna Raychaudhuri, Snehal Mahadik, Divya Reddy, Apurva Atak, Trupti Shetty, Kruthi Rao, Mansi S Karkhanis, Prajakta Gosavi, Lalit Sehgal, Sanjay Gupta, Sorab N Dalal
Previous reports show that the desmosomal plaque protein plakophilin3 (PKP3) is essential for desmosome formation. Here, we report that PKP3 over-expression decreases calcium dependency for de novo desmosome formation and makes existing cell-cell adhesion junctions more resilient in low calcium medium due to an increase in desmocollin2 expression. PKP3 overexpression increases the stability of other desmosomal proteins independently of the increase in DSC2 levels and regulates desmosome formation and stability by a multimodal mechanism affecting transcription, protein stability and cell border localization of desmosomal proteins...
November 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29111817/structural-ultrastructural-and-morphometric-study-of-the-zebrafish-ocular-surface-a-model-for-human-corneal-diseases
#15
Domenico Puzzolo, Antonina Pisani, Consuelo Malta, Giuseppe Santoro, Alessandro Meduri, Francesco Abbate, Giuseppe Montalbano, Edward Wylegala, Rosa Alba Rana, Fabio Bucchieri, Antonio Ieni, Pasquale Aragona, Antonio Micali
PURPOSE: A morphological and morphometric study of the adult zebrafish ocular surface was performed to provide a comprehensive description of its parts and to evaluate its similarity to the human. MATERIALS AND METHODS: The eyes of adult zebrafish were processed for light, transmission and scanning electron microscopy, and for immunohistochemical stain of corneal nerves; a morphometric analysis was also performed on several morphological parameters. RESULTS: The corneal epithelium was formed by five layers of cells...
November 7, 2017: Current Eye Research
https://www.readbyqxmd.com/read/29092692/characterization-of-multi-layered-tissue-engineered-human-alveolar-bone-and-gingival-mucosa
#16
Thafar Almela, Sarmad Al-Sahaf, Robert Bolt, Ian Brook, K Moharamzadeh
Advances in tissue engineering have permitted assembly of multi-layered composite tissue constructs for potential applications in the treatment of combined hard and soft tissue defects and as an alternative in vitro test model to animal experimental systems. The aim of this study was to develop and characterize a novel three-dimensional combined human alveolar bone and gingival mucosal model based on primary cells isolated from the oral tissues. Bone component of the model was engineered by seeding primary human alveolar osteoblasts (HAOBs) into a hydroxyapatite/tricalcium phosphate (HA/TCP) scaffold and culturing in a spinner bioreactor...
November 1, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/29062102/arrhythmogenic-cardiomyopathy-related-dsg2-mutations-affect-desmosomal-cadherin-binding-kinetics
#17
Mareike Dieding, Jana Davina Debus, Raimund Kerkhoff, Anna Gaertner-Rommel, Volker Walhorn, Hendrik Milting, Dario Anselmetti
Cadherins are calcium dependent adhesion proteins that establish the intercellular mechanical contact by bridging the gap to adjacent cells. Desmoglein-2 (Dsg2) is a specific cadherin of the cell-cell contact in cardiac desmosomes. Mutations in the DSG2-gene are regarded to cause arrhythmogenic (right ventricular) cardiomyopathy (ARVC) which is a rare but severe heart muscle disease. The molecular pathomechanisms of the vast majority of DSG2 mutations, however, are unknown. Here, we investigated the homophilic binding of wildtype Dsg2 and two mutations which are associated with ARVC...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051189/klf-5-extends-its-fingers-to-desmosomes-the-next-frontier-for-enteric-epithelial-research
#18
Narek Israelyan, Kara Gross Margolis
n/a.
October 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29044515/the-human-pkp2-plakophilin-2-gene-is-induced-by-wnt-%C3%AE-catenin-in-normal-and-colon-cancer-associated-fibroblasts
#19
Núria Niell, María Jesús Larriba, Gemma Ferrer-Mayorga, Isabel Sánchez-Pérez, Ramón Cantero, Francisco X Real, Luis Del Peso, Alberto Muñoz, José Manuel González-Sancho
Colorectal cancer results from the malignant transformation of colonic epithelial cells. Stromal fibroblasts are the main component of the tumour microenvironment, and play an important role in the progression of this and other neoplasias. Wnt/β-catenin signalling is essential for colon homeostasis, but aberrant, constitutive activation of this pathway is a hallmark of colorectal cancer. Here we present the first transcriptomic study on the effect of a Wnt factor on human colonic myofibroblasts. Wnt3A regulates the expression of 1,136 genes, of which 662 are upregulated and 474 are downregulated in CCD-18Co cells...
October 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29043097/histological-study-on-the-effect-of-nicotine-on-adult-male-guinea-pig-thin-skin
#20
Sohair A Eltony, Safaa S Ali
Tobacco smoking has been identified as an important factor in premature skin aging to detect the histological changes occurred in adult male guinea pig thin skin under the influence of low and high doses of nicotine; which constitutes approximately 0.6%-3.0% of the dry weight of tobacco. Fifteen adult male pigmented guinea pigs were equally divided into three groups: group I, control; group IIA, low dose nicotine treated; 3 mg/kg subcutaneously for 4 weeks; and group IIB, high dose nicotine treated; 6 mg/kg subcutaneously for 4 weeks...
September 2017: Anatomy & Cell Biology
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