Plakophilin 2 regulates intestinal barrier function by modulating protein kinase C activity in vitro

Nagler, Simon; Ghoreishi, Yalda; Kollmann, Cathérine; Kelm, Matthias; Gerull, Brenda; Waschke, Jens; Burkard, Natalie; Schlegel, Nicolas

doi:10.1080/21688370.2022.2138061

Cited by 7 publications

(13 citation statements)

References 39 publications

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“…The PKP2 R388W variant was identified in this case. PKP2 encodes plakophilin2, a member of the armadillo family proteins, which plays an important role in regulating desmosome function and cell adhesion 26 . This variant has been reported in two different families with arrhythmogenic right ventricular cardiomyopathy, 27,28 and therefore ClinVar has annotated this variant as Pathogenic/Likely_pathogenic.…”

Section: Discussionmentioning

confidence: 99%

“…PKP2 encodes plakophilin2, a member of the armadillo family proteins, which plays an important role in regulating desmosome function and cell adhesion. 26 This variant has been reported in two different families with arrhythmogenic right ventricular cardiomyopathy, 27,28 and therefore ClinVar has annotated this variant as Pathogenic/Likely_ pathogenic. However, the PKP2 R388W mutation in cancer is extremely rare; only one in 70 655 cases harbors the PKP2 R388W mutation based on cBioportal.…”

Section: Discussionmentioning

confidence: 99%

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Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing

Takeda,

Makise,

Lin

et al. 2024

Genes Chromosomes & Cancer

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Dermatofibroma (DF) is a benign tumor that forms pedunculated lesions ranging in size from a few millimeters to 2 cm, usually affecting the extremities and trunks of young adults. Histopathologically, DF is characterized by the storiform proliferation of monomorphic fibroblast‐like spindle cells. In addition to neoplastic cells, secondary elements such as foamy histiocytes, Touton‐type giant cells, lymphoplasmacytes, and epidermal hyperplasia are characteristic histological features. Several histological variants, including atypical, cellular, aneurysmal, and lipidized variants, have been reported; cases with variant histologies are sometimes misdiagnosed as sarcomas. We present a case of metastasizing aneurysmal DF that was initially diagnosed as an angiosarcoma on biopsy. A 26‐year‐old woman was referred to our hospital with a gradually enlarging subcutaneous mass in her lower left leg. Positron emission tomography‐computed tomography revealed high fluorodeoxyglucose uptake not only in the tumor but also in the left inguinal region. On biopsy, ERG and CD31‐positive atypical spindle cells proliferated in slit‐like spaces with extravasation, leading to the diagnosis of angiosarcoma. Histology of the wide‐resection specimen was consistent with DF, and lymph node metastasis was also observed. Nanopore DNA sequencing detected CD63::PRKCD fusion and copy number gain, although CD63 was not included in the target region of adaptive sampling. This report highlights the importance of recognizing the unusual clinical, radiological, and pathological features of DF to avoid misdiagnosis, and the potential diagnostic utility of nanopore sequencer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing

Takeda,

Makise,

Lin

et al. 2024

Genes Chromosomes & Cancer

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“…This plaque is then linked to the cytoskeleton via desmoplakin [ 8 ]. Desmosomes provide resistance to mechanical stress [ 9 ], but they are also involved in managing intestinal permeability by creating strong cell–cell bonds and stabilising tight junctions [ 10 , 11 ].…”

Section: Key Elements In Barrier Permeabilitymentioning

confidence: 99%

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

Schreiber,

Balas,

Robinson

et al. 2024

Cells

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The gut mucosal epithelium is one of the largest organs in the body and plays a critical role in regulating the crosstalk between the resident microbiome and the host. To this effect, the tight control of what is permitted through this barrier is of high importance. There should be restricted passage of harmful microorganisms and antigens while at the same time allowing the absorption of nutrients and water. An increased gut permeability, or “leaky gut”, has been associated with a variety of diseases ranging from infections, metabolic diseases, and inflammatory and autoimmune diseases to neurological conditions. Several factors can affect gut permeability, including cytokines, dietary components, and the gut microbiome. Here, we discuss how the gut microbiome impacts the permeability of the gut epithelial barrier and how this can be harnessed for therapeutic purposes.

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“…The junctional complexes are located at the apical regions of the lateral membranes of cells and consist of tight junctions, adherens junctions and desmosomes [ 135 , 136 ]. The contributions of adherens junctions [ 137 , 138 , 139 ] and desmosomes to barrier function are well recognized [ 140 , 141 , 142 , 143 , 144 ]. However, tight junctions (TJs) act as the critical determinants of intestinal epithelial barrier integrity [ 135 ].…”

Section: Adenosine Reinforces Epithelial Tight Junctionsmentioning

confidence: 99%

“…In this branch, the role of the adenosine–PKA–VASP axis in the recruitment of tight junction proteins (claudins, occludins and JAMs) and adherens junction proteins (cadherins, catenins) remains to be explored. Desmosome dysregulation is also implicated in IBD and their contributions to barrier function are not negligible [ 140 , 141 , 142 , 143 , 144 , 171 ]. Addressing the interplay of adenosine signaling with desmosome formation would resolve the knowledge gap in the field.…”

Section: Adenosine Reinforces Epithelial Tight Junctionsmentioning

confidence: 99%

Adenosine in Intestinal Epithelial Barrier Function

Stepanova,

Aherne

2024

Cells

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At the intestinal front, several lines of defense are in place to resist infection and injury, the mucus layer, gut microbiome and strong epithelial junctions, to name a few. Their collaboration creates a resilient barrier. In intestinal disorders, such as inflammatory bowel disease (IBD), barrier function is compromised, which results in rampant inflammation and tissue injury. In response to the destruction, the intestinal epithelium releases adenosine, a small but powerful nucleoside that functions as an alarm signal. Amidst the chaos of inflammation, adenosine aims to restore order. Within the scope of its effects is the ability to regulate intestinal epithelial barrier integrity. This review aims to define the contributions of adenosine to mucus production, microbiome-dependent barrier protection, tight junction dynamics, chloride secretion and acid–base balance to reinforce its importance in the intestinal epithelial barrier.

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Plakophilin 2 regulates intestinal barrier function by modulating protein kinase C activity in vitro

Cited by 7 publications

References 39 publications

Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing

Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

Adenosine in Intestinal Epithelial Barrier Function

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