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The cardiovascular system
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Mary N Sheppard, C. Simon Herrington
Arrhythmogenic cardiomyopathy is now regarded as a genetically determined myocardial degenerative disease. It is inherited in an autosomal dominant manner but autosomal recessive forms (e.g. Naxos and Carvajal syndromes caused by mutations in genes encoding plakoglobin [JUP] and desmoplakin [DSP], respectively are recognized). It was the discovery of the genetic basis of Naxos disease that led to the disease being largely due to mutations in desmosomal proteins, which are important in cell-to-cell adhesion, including desmoplakin (DSP), plakophilin-2 (PKP2), desmoglein-2 (DSG2), and desmocolin-2 (DSC2), all of which cause autosomal-dominant forms of AC. Mutations in genes encoding non-desmosomal proteins have also been identified. Most are associated with other cardiomyopathies and arrhythmia syndromes and represent phenotypic overlap. These include the intermediate filament protein desmin (DES), the cardiac sodium channel − Nav 1.5 (SCN5A), lamin A/C (LMNA) on the nuclear membrane, titin (TTN), phospholamban (PLN), and filamin C (FLNC). Pathogenic variants in genes encoding α-T-Catenin (CTNNA3) and N-cadherin (CDH2) have been identified in a small group of AC patients with typical right-predominant disease. The pS358L founder mutation in TMEM43, encoding transmembrane protein 43 is common among French Canadian AC patients. Mutations in transforming growth factor beta-3 (TGFB3) have been described but association with AC remains to be confirmed.
Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Activation of RAR and PPAR by RA is crucial for induction of neuronal differentiation, and various target genes have been reported to be involved in this process (25,26). RA, through its effectors, directly regulates expression of subset of homeotic genes (Hox) Hoxa-1, Hoxb-2, and Wnt-1 (27). These master control genes specify the body plan and regulate the development and morphogenesis of higher organisms. In addition, RA also indirectly regulates achaete-scute family bHLH transcription factor 1 gene (ASCL1), Neurogenin 1 (NEUROG1), neuronal differentiation 1 (NeuroD1), N-cadherin/cadherin 2 (CDH2), and pre-B-cell leukemia transcription factors or PBX homeobox genes (Pbx) (7).
Chemical Causes of Cancer
Published in Peter G. Shields, Cancer Risk Assessment, 2005
Gary M. Williams, Alan M. Jeffrey
Each type of malignancy has a specific pattern of metastasis which is determined both by lymphatic and blood drainage from the tumor, and also by factors produced by disseminated cells allowing them to establish metastases (157,158). Genes regulating metastasis of tumor cells have been categorized as either metastasis-promoting (CDH2, CXCRy, MTA1) or metastasis-suppressing (CD9, CD44, Nm 23, KiSS1, Ka11/CD82, CDH1,MAP2K4, MKK4, TIMP, and BRMS1) (159). Several of these (CD9,CD44, and CD82) code for transmembrane proteins. One possible mechanism for metastasis inhibition is the maintenance of gap junction intracellu-lar communication (160).
Bioinformatics analyses reveal cell-barrier junction modulations in lung epithelial cells on SARS-CoV-2 infection
Published in Tissue Barriers, 2022
Mir S. Adil, Daulat Khulood, S. Priya Narayanan, Payaningal R. Somanath
With the help of the miRNA database, we determined if miRNAs influence the observed changes in cytoskeletal and cell-barrier junction-related genes. The only microRNA from NHBE, miR503, demonstrated no link with cytoskeletal and cell junctions related genes. Interestingly, Calu-3 cells revealed a probable cause of ICAM1 upregulation associated with the observed increase in the expression level of miR612. Furthermore, the analysis remarkably disclosed direct links between 7 miRNAs and 12 cytoskeletal and cell–cell barrier junctions related genes (Figure 5). Intriguingly, miR4263 was found to be associated only with A549 cell-line genes despite being modulated in both A549 and Calu-3 cell lines. Further, all miRNAs, except the miR3176, were found to be upregulated upon CoV-2 infection in our analyses. Some significant associations from the study include CDH2 upregulation by miR450A1 and increased CLDN-4 and −12 expression through miR-3189 and −221, respectively.
The role of the prolactin receptor pathway in the pathogenesis of glioblastoma: what do we know so far?
Published in Expert Opinion on Therapeutic Targets, 2020
Antonela S Asad, Alejandro J Nicola Candia, Nazareno Gonzalez, Camila F Zuccato, Adriana Seilicovich, Marianela Candolfi
Although PRLR expression levels showed no correlation with the expression of CDH1 gene (Figure 1C), which encodes for E-cadherin, it negatively correlates with the expression of CDH2 gene (Figure 1D), which codifies for neural cadherin (N-cadherin). E-cadherine and N-cadherine are traditionally associated with EMT [98]. Although in carcinomas, such as breast cancer, the loss of E-cadherin decreases cell polarization and induces EMT and tumor invasion, classical cadherin contribution to non-epithelial tumor development is not clear and remains controversial [99,100]. Even though E-cadherin is the most important factor involved in cell-to-cell contact, it is rarely expressed in GBM [94]. On the other hand, N-cadherin modulates cells polarity and migration by the regulation of cellular focal adhesion [101]. Lower grade gliomas usually exhibit lower levels of N-cadherin that seems to be associated with a faster migration [101]. Indeed, N-cadherin re-expression in GBM cells restores cell polarity and decelerates the speed of migration, suggesting that the loss of N-cadherin expression enhances GBM cell invasion [101]. Taken together, all these observations suggest that the expression of PRLR could be associated with the process of EMT in gliomas.
Involvement of β-catenin in Androgen-induced Mesenchymal Transition of Breast MDA-MB-453 Cancer Cells
Published in Endocrine Research, 2021
Mamoun Ahram, Randa Bawadi, Mohammad S. Abdullah, Dana B. Alsafadi, Haneen Abaza, Sallam Abdallah, Ebtihal Mustafa
DHT induction of AR translocation into the nucleus and the delayed effect of DHT on the mesenchymal transition of cells suggest that DHT alters the expression of EMT-regulatory genes. Therefore, the expression of 84 EMT-related genes was examined using PCR arrays following treatment of MDA-MB-453 cells with 100 nM DHT for 72 or 144 hrs. The concentration of DHT and duration of treatments were selected since the mesenchymal phenotype was maximal at these conditions allowing for the measurement of, presumably, the highest change of gene expression. In addition, previous work has shown little change in the expression of many of these genes after 24 hrs of treatment.34 The results of the PCR array showed that 23 genes were dysregulated by ≥2 folds at 72 and/or 144 hrs (Table 1). Expression of all 84 genes can be seen in Table 2S. Expression of four genes (TCF-4, CDH2, FN1, and CAMK2N1) was down-regulated after 72 or 144 hrs of treatment. The down-regulation of TCF-4 was particularly noticeable at both time points. CDH2 was slightly reduced after 72 hrs of treatment, only to be considerably down-regulated at the longer exposure. Interestingly, these four genes are known to be up-regulated in mesenchymal cells. β-catenin (CTNNB1), another marker of mesenchymal cells, was down-regulated significantly by 30 folds only after long exposure to DHT. RGS2, SNAI2 (Slug), AHNAK, and EGFR were found to be up-regulated at both periods of treatments. Whereas SNAI2, AHNAK, and EGFR are pro-EMT, RGS2 is known to be down-regulated in mesenchymal cells.40,41 E-cadherin (CDH1), an epithelial marker, was not dysregulated at either time point, and vimentin, a mesenchymal marker, was not expressed in these cells (Table 2S).