Desmosome

BACKGROUND: Radiofrequency (RF)-based devices are frequently used in plastic surgeries. In the current literature, no comparative experimental study has demonstrated the histological and immunological effects of these devices that are frequently used in the facial area. In this study, we investigated the histological and immunological effects of Bipolar RF (BodyTite) and Microneedle RF (Morpheus 8) devices in the rat abdominal region. METHODS: 24 rats were used in this study...

Pemphigus is a severe blistering disease caused by autoantibodies primarily against the desmosomal cadherins desmoglein (DSG)1 and DSG3 which impair desmosome integrity. Especially for the acute phase, additional treatment options allowing to reduce corticosteroids would fulfill an unmet medical need. Here, we provide evidence that epidermal growth factor receptor (EGFR) inhibition by erlotinib ameliorates pemphigus vulgaris immunoglobulin G (PV-IgG) -induced acantholysis in intact human epidermis. PV-IgG caused phosphorylation of EGFR (Y845) and SRC in human epidermis...

The Notch signaling pathway plays a pivotal role in governing cell fate determinations within the gonadal niche. This study provides an extensive elucidation of the male and female gonadal niches within Crassostrea gigas. Examination via transmission electron microscopy revealed the presence of desmosome-like connection not only between germ cells and niche cells but also among adjacent niche cells within the oyster gonad. Transcriptomic analysis identified several putative Notch pathway components, including CgJAG1, CgNOTCH1, CgSuh, and CgHey1...

UNLABELLED: This study aimed to determine the prevalence and clinical features of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) caused by pathogenic mutations in the Phospholamban ( PLN ) gene. The study included 170 patients who had a confirmed diagnosis of ARVC and underwent PLN genetic screening using next-generation sequencing. The findings of this study provide valuable insights into the association between PLN mutations and ARVC, which can aid in the development of more effective diagnostic and treatment strategies for ARVC patients...

PURPOSE: Diabetic macular edema (DME) is a sight-threatening complication of diabetes. Consequently, studying the proteome of DME may provide novel insights into underlying molecular mechanisms. METHODS: In this study, aqueous humor samples from eyes with treatment-naïve clinically significant DME (n = 13) and age-matched controls (n = 11) were compared with label-free liquid chromatography-tandem mass spectrometry. Additional aqueous humor samples from eyes with treatment-naïve DME (n = 15) and controls (n = 8) were obtained for validation by enzyme-linked immunosorbent assay (ELISA)...

BACKGROUND: Acute myocarditis is an inflammatory condition that may precede the development of dilated or arrhythmogenic cardiomyopathy. OBJECTIVES: The aim of this study was to investigate the reported prevalence of pathogenic or likely pathogenic (P/LP) variants in cardiomyopathy-associated genes in patients with acute myocarditis. METHODS: For this systematic review and meta-analysis, the PubMed and Embase databases were searched on March 4, 2023...

Desmosomes are intercellular junctions that regulate mechanical integrity in epithelia and cardiac muscle. Dynamic desmosome remodeling is essential for wound healing and development, yet the mechanisms governing junction assembly remain elusive. While we and others have shown that cadherin ectodomains are highly organized, how this ordered architecture emerges during assembly is unknown. Using fluorescence polarization microscopy, we show that desmoglein 2 (Dsg2) ectodomain order gradually increases during 8 h of assembly, coinciding with increasing adhesive strength...

Cluster of differentiation 109 (CD109) is a glycosylphosphatidylinositol (GPI) anchored cell surface protein, expressed on epithelial and endothelial cells, CD4+ and CD8+ T-cells, and premature lymphocytes. CD109 interacts with different cell surface receptors and thereby modulates intracellular signaling pathways, which ultimately changes cellular functions. One well-studied example is the interaction of CD109 with the TGFβ/TGFβ-receptor complex at the cell surface. CD109 silences intracellular SMAD2/3 signaling and targets TGFβ/TGFβ-receptor to the endosomal/lysosomal compartment...

Genetic cardiomyopathies (CM) are disorders that affect morphology and function of cardiac muscle. Significant number of genes have been implicated in causing the phenotype. It is one of the leading genetic causes of death in young. We performed a study to understand the genetic variants in primary cardiomyopathies in an Indian cohort. Study comprised of 22 probands (13 with family history) representing hypertrophic (n = 10), dilated (n = 7), restrictive (n = 2) and arrhythmogenic ventricular(n = 3) cardiomyopathies...

From the moment a cell is on the path to malignant transformation, its interaction with other cells from the microenvironment becomes altered. The flow of molecular information is at the heart of the cellular and systemic fate in tumors, and various processes participate in conveying key molecular information from or to certain cancer cells. For instance, the loss of tight junction molecules is part of the signal sent to cancer cells so that they are no longer bound to the primary tumors and are thus free to travel and metastasize...

Arrhythmogenic cardiomyopathy (ACM) is a genetic disease characterized by replacement of ventricular myocardium with fibrofatty tissue, predisposing the patient to ventricular arrhythmias and/or sudden cardiac death. Most cases of ACM are associated with pathogenic variants in genes that encode desmosomal proteins, an important cell-to-cell adhesion complex present in both the heart and skin tissue. Although ACM was first described as a disease predominantly of the right ventricle, it is now acknowledged that it can also primarily involve the left ventricle or both ventricles...

Desmoplakin (DSP) is a desmosomal component expressed in skin and heart, essential for desmosome stability and intermediate filament connection. Pathogenic variants in the DSP gene encoding DSP, lead to heterogeneous skin, adnexa and heart-related phenotypes, including skin fragility, woolly hair (WH), palmoplantar keratoderma (PPK) and arrhythmogenic/dilated cardiomyopathy (ACM/DCM). The ambiguity of computer-based prediction analysis of pathogenicity and effect of DSP variants, indicates a necessity for functional analysis...

Pemphigus vulgaris is a rare autoimmune bullous disease characterized by blistering of the skin and mucosa owing to the presence of autoantibodies against the desmosome proteins desmoglein 3 and occasionally in conjunction with desmoglein 1. Fundamental research into the pathogenesis of PV has revolutionized its treatment and outcome with rituximab, a B-cell-depleting therapy. The critical contribution of B cells to the pathogenesis of pemphigus is well accepted. However, the exact pathomechanism, mechanisms of onset, disease course, and relapse remain unclear...

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Currently, there are no approved treatments that address the underlying genetic cause of this disease, representing a significant unmet need. Mutations in Plakophilin-2 (PKP2), encoding a desmosomal protein, account for approximately 40% of ARVC cases and result in reduced gene expression. METHODS: Our goal is to examine the feasibility and the efficacy of adeno-associated virus 9 (AAV9)-mediated restoration of PKP2 expression in a cardiac specific knock-out mouse model of Pkp2...

In this study, we explore the impact of mechanical stimuli on skin models using an innovative skin-on-a-chip platform, addressing the limitations of conventional transwell-cultured skin equivalents. This platform facilitates cyclic mechanical stimulation through compression and stretching, combined with automated media perfusion. Our findings, using bioimaging and bulk RNA sequencing, reveal increased expression of Keratin 10 and Keratin 14, indicating enhanced skin differentiation and mechanical integrity...

BACKGROUND: Arrhythmogenic ventricular cardiomyopathy (AVC) is a hereditary cardiomyopathy that has been associated with mutations in genes encoding for components of the cardiac desmosome including desmoglein-2 (DSG-2). CASE SUMMARY: A 49-year-old male presented with decompensated heart failure and ventricular arrythmias. A cardiac magnetic resonance scan demonstrated a dilated left ventricle (LV) with severely impaired systolic function and extensive subepicardial late gadolinium enhancement in the lateral wall...

Glycosylation is essential to facilitate cell-cell adhesion and differentiation. We determined the role of the dolichol phosphate mannosyltransferase (DPM) complex, a central regulator for glycosylation, for desmosomal adhesive function and epidermal differentiation. Deletion of the key molecule of the DPM complex, DPM1, in human keratinocytes resulted in weakened cell-cell adhesion, impaired localization of the desmosomal components desmoplakin and desmoglein-2, and led to cytoskeletal organization defects in human keratinocytes...

Engineered heart tissues have been created to study cardiac biology and disease in a setting that more closely mimics in vivo heart muscle than 2D monolayer culture. Previously published studies suggest that geometrically anisotropic micro-environments are crucial for inducing " in vivo like" physiology from immature cardiomyocytes. We hypothesized that the degree of cardiomyocyte alignment and prestress within engineered tissues is regulated by tissue geometry and, subsequently, drives electrophysiological development...

BACKGROUND: Thousands of genetic variants have been identified in cardiomyopathy-associated genes. Diagnostic genetic testing is key for evaluation of individuals with suspected cardiomyopathy. While accurate variant pathogenicity assignment is important for diagnosis, the frequency of and factors associated with clinically relevant assessment changes are unclear. OBJECTIVES: The authors aimed to characterize pathogenicity assignment change in cardiomyopathy-associated genes and to identify factors associated with this change...

Previous studies have implicated persistent innate immune signaling in the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a familial non-ischemic heart muscle disease characterized by life-threatening arrhythmias and progressive myocardial injury. Here, we provide new evidence implicating inflammatory lipid autocoids in ACM. We show that specialized pro-resolving lipid mediators are reduced in hearts of Dsg2mut/mut mice, a well characterized mouse model of ACM. We also found that ACM disease features can be reversed in rat ventricular myocytes expressing mutant JUP by the pro-resolving epoxy fatty acid (EpFA) 14,15-eicosatrienoic acid (14-15-EET), whereas 14,15-EE-5(Z)E which antagonizes actions of the putative 14,15-EET receptor, intensified nuclear accumulation of the desmosomal protein plakoglobin...