Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence

Lluch, Aina; Latorre, Jessica; Serena-Maione, Angela; Espadas, Isabel; Caballano-Infantes, Estefanía; Moreno-Navarrete, José M.; Oliveras-Cañellas, Núria; Ricart, Wifredo; Malagón, María M.; Martin-Montalvo, Alejandro; Birchmeier, Walter; Szymanski, Witold; Graumann, Johannes; Gómez-Serrano, María; Sommariva, Elena; Fernández-Real, José M.; Ortega, Francisco J.

doi:10.1038/s41467-023-40596-0

Cited by 6 publications

(2 citation statements)

References 100 publications

(152 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Altered expression of PCSK9 [72], CNTN4 [49], SEMA3A [73], SFRP4 [74], MFAP5 [75], BMP6 [76], PDE1C [77] and PKP2 [78] promotes the development of cardiovascular diseases. PCSK9 [79], APCDD1 [80], SFRP4 [81], MFAP5 [82] and PKP2 [83] are associated to the risk of obesity. Studies show that PCSK9 [84] and SFRP4 [85] are involved in the process of gestational diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

View full text Add to dashboard Cite

Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis. Next generation sequencing (NGS) dataset GSE243039 was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein-protein interaction (PPI) network was constructed and modules were analysed using the Human Integrated Protein-Protein Interaction rEference (HIPIE) database and Cytoscape software, and hub genes were identified. Subsequantely, a network between miRNAs and hub genes, and network between TFss and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve (ROC) analysis was used to validate the hub genes. A total of 958 DEGs, including 479 up regulated genes and 479 down regulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including VCAM1, SNCA, PRKCB, ADRB2, FOXQ1, MDFI, ACTBL2, PRKD1, DAPK1 and ACTC1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including TCF3 and CLOCK, were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment, and monitoring of endometriosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Previous research studies have expanded our understanding of the role of adipocyte senescence in obesity [10][11][12]. Research shows that senescent adipocytes are susceptible to genome instability, leading to unhealthy adipose tissue remodeling and insulin resistance [11].…”

Section: Introductionmentioning

confidence: 99%

Ex vivo Anti-Senescence Activity of N-Acetylcysteine in Visceral Adipose Tissue of Obese Volunteers

Behtaj,

Ghorbani,

Eslamian

et al. 2024

Obes Facts

View full text Add to dashboard Cite

Introduction: Excessive visceral adiposity is known to drive the onset of metabolic derangements, mostly involving oxidative stress, prolonged inflammation and cellular senescence. N-acetyl cysteine (NAC) is a synthetic form of L-cysteine with potential antioxidant, anti-inflammatory, and anti-senescence properties. This ex-vivo study aimed to determine the effect of NAC on some markers of senescence including β-galactosidase activity and p16, p53, p21, IL-6 and TNF-α gene expressions in visceral adipose tissue in obese adults. Methods: This ex-vivo experimental study involved 10 obese participants who were candidates for bariatric surgery. Duplicate biopsies from the abdominal visceral adipose tissue were obtained from the omentum. The biopsies were treated with or without NAC (5 and 10 mM). To evaluate adipose tissue senescence, beta-galactosidase (β-gal) activity and the expression of P16, P21, P53, IL-6, and TNF-α were determined. ANOVA test was employed to analyze the varying markers of cellular senescence and inflammation between treatment groups. Results: The NAC at concentrations of 5 mM and 10 mM resulted in a noteworthy reduction β-gal activity compared to the control group (P < 0.001). Additionally, the expression of P16, P21 and IL-6 was significantly reduced following treatment with NAC (5 mM) and NAC (10 mM) compared to the control group (All p<0.001). Discussion/Conclusion: Taken together, these data suggest the senotherapeutic effect of NAC, as it effectively reduces the activity of SA-β-gal and the expression of IL-6, P16, and P21 genes in the visceral adipose tissue of obese individuals.

show abstract

Plakoglobin regulates adipocyte differentiation independently of the Wnt/β-catenin signaling pathway

Abou Azar,

Mugabo,

Yuen

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence

Cited by 6 publications

References 100 publications

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

Ex vivo Anti-Senescence Activity of N-Acetylcysteine in Visceral Adipose Tissue of Obese Volunteers

Plakoglobin regulates adipocyte differentiation independently of the Wnt/β-catenin signaling pathway

Contact Info

Product

Resources

About