Short interfering RNAs (siRNAs)-based knockdown of OLFM2 or PKP2 in human adipocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE182231 | GEO | 2021/12/28
REPOSITORIES: GEO
Similar Datasets
Project description:We introduced into subcutaneous fully-differentiated human adipocytes from the same subject small hairpin RNAs (shRNAs) against two genes, thus enabling the study of functional consequences of sustained OLFM2 (shOLFM2; n=3 biological replicates) and PKP2 (shPKP2; n=3) knockdown in these cells. The lentiviral-based transfection was used to provide a long-lasting, convenient, reliable and efficient knockdown into in vitro cultured and fully differentiated adipocytes maintained for 6 d after reaching fully differentiation. A non-targeting shRNA was used as control (shCTRL; n=4) and reference for both modifications.
2021-12-28 | GSE182229 | GEO
Project description:Short interfering RNAs (siRNAs)-based knockdown of OLFM2 or PKP2 in human adipocytes
| PRJNA755338 | ENA
Project description:To explore the downstream genes of PKP2,we performed RNA-seq to screen after overexpression of PKP2 in A549 cells.
2023-08-05 | GSE155759 | GEO
Project description:Plakophilin2 (PKP2) is a key component of desmosomes mostly recognized for its involvement in the fibro fatty infiltration of heart muscle under defective PKP2. While thoroughly explored in cardiomyocytes, less attention has been given to its role in fat cells. Here we report steadily increased PKP2 during adipogenesis, with expression levels reaching its apex in terminally differentiated adipocytes. Notably, the loss of this protein in adipocytes under a pro-inflammatory microenvironment demonstrates its commitment in maintaining the expression of genes required to nurture cell cycle. Then, we show that diminished expressions of this member of the armadillo repeat family in subcutaneous adipose tissue co-segregate with obesity, being normalized upon mild to intense weight loss. We also demonstrate that impaired PKP2 in human adipocytes breaks cell cycle dynamics to breed premature senescence, a key rheostat for stress induced adipose tissue dysfunction. Conversely, restoring PKP2 in inflamed adipocytes rewires E2F signalling towards re-activation of cell cycle and decreased senescence. Our findings bound the expression of PKP2 in fat cells to the physiopathology of obesity, and uncover a previously unknown defect in cell cycle and activated adipocyte senescence due to impaired PKP2.
2023-05-10 | MSV000091898 | MassIVE
Project description:TCP1 papillary thyroid carcinoma cells were plated at 100,000 cells/well in a 6-well plate and transfected with 10nM of a synthetic pre-miR-129-5p or a negative pre-miRNA using Lipofectamine RNAiMAX reagent. RNA samples were harvested at 24 and 48 hours post-transfection.
2011-12-06 | GSE19933 | GEO
Project description: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. Results: We show that a single dose of AAV9:PKP2 gene delivery prevents disease development before the onset of cardiomyopathy and attenuates disease progression after overt cardiomyopathy. Restoration of PKP2 expression leads to a significant extension of lifespan by restoring cellular structures of desmosomes and gap junctions, preventing or halting decline in left ventricular ejection fraction, preventing or reversing dilation of the right ventricle, ameliorating ventricular arrhythmia event frequency and severity, and preventing adverse fibrotic remodeling. RNA sequencing analyses show that restoration of PKP2 expression leads to highly coordinated and durable correction of PKP2-associated transcriptional networks beyond desmosomes, revealing a broad spectrum of biological perturbances behind ARVC disease etiology. Conclusions: We identify fundamental mechanisms of PKP2-associated ARVC beyond disruption of desmosome function. The observed PKP2 dose-function relationship indicates that cardiac-selective AAV9:PKP2 gene therapy may be a promising therapeutic approach to treat ARVC patients with PKP2 mutations.
2024-02-23 | GSE253223 | GEO
Project description: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. Results: We show that a single dose of AAV9:PKP2 gene delivery prevents disease development before the onset of cardiomyopathy and attenuates disease progression after overt cardiomyopathy. Restoration of PKP2 expression leads to a significant extension of lifespan by restoring cellular structures of desmosomes and gap junctions, preventing or halting decline in left ventricular ejection fraction, preventing or reversing dilation of the right ventricle, ameliorating ventricular arrhythmia event frequency and severity, and preventing adverse fibrotic remodeling. RNA sequencing analyses show that restoration of PKP2 expression leads to highly coordinated and durable correction of PKP2-associated transcriptional networks beyond desmosomes, revealing a broad spectrum of biological perturbances behind ARVC disease etiology. Conclusions: We identify fundamental mechanisms of PKP2-associated ARVC beyond disruption of desmosome function. The observed PKP2 dose-function relationship indicates that cardiac-selective AAV9:PKP2 gene therapy may be a promising therapeutic approach to treat ARVC patients with PKP2 mutations.
2024-02-23 | GSE253224 | GEO
Project description: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. Results: We show that a single dose of AAV9:PKP2 gene delivery prevents disease development before the onset of cardiomyopathy and attenuates disease progression after overt cardiomyopathy. Restoration of PKP2 expression leads to a significant extension of lifespan by restoring cellular structures of desmosomes and gap junctions, preventing or halting decline in left ventricular ejection fraction, preventing or reversing dilation of the right ventricle, ameliorating ventricular arrhythmia event frequency and severity, and preventing adverse fibrotic remodeling. RNA sequencing analyses show that restoration of PKP2 expression leads to highly coordinated and durable correction of PKP2-associated transcriptional networks beyond desmosomes, revealing a broad spectrum of biological perturbances behind ARVC disease etiology. Conclusions: We identify fundamental mechanisms of PKP2-associated ARVC beyond disruption of desmosome function. The observed PKP2 dose-function relationship indicates that cardiac-selective AAV9:PKP2 gene therapy may be a promising therapeutic approach to treat ARVC patients with PKP2 mutations.
2024-02-23 | GSE253225 | GEO
Project description:Plakophilin 2 (PKP2), encodes a plakophilin protein that belongs to the member of desmosomal proteins.PkP2 regulates some cell biological functions, but its downstream genes are not clear, so we constructed a stable cell line using H460 cells and identified its downstream target genes by RNA-seq technology
2022-11-13 | GSE140509 | GEO
Project description:Summary: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder. It is classified as the second most common cause of unexpected sudden death by cardiac arrest in the young. ARVC has devastating psychosocial consequences, especially as many patients are young adults, and current therapy is limited to extreme exercise restriction and defibrillator implantation. More than 40% of the reported genetic variants linked to ARVC reside in a gene called PKP2 , which encodes for the plakophilin-2 (PKP2) protein. The pathogenic mechanisms linking this protein to ARVC remain to be elucidated, which is the focus of this project. I aim to identify exactly which proteins in the heart are dysregulated and to identify why exercise is detrimental for carriers of PKP2-deficient hearts. Our approach is based on state-of-the-art mass spectrometry (MS) technologies that allow us to measure all proteins in the heart simultaneously. We used both human heart biopsy material as well as a murine disease model I anticipate to elucidate novel roles of PKP2 that are of utmost importance for understanding ARVC pathogenesis.
2022-11-04 | PXD025523 | Pride