Adipocyte deletion of the RNA binding protein HuR induces cardiac hypertrophy and fibrosis DOI Open Access

Adrienne Guarnieri,

Sarah Anthony,

Anamarie Gozdiff

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Jan. 19, 2021

ABSTRACT Adipose tissue continues to gain appreciation for its broad role as an endocrine organ, and disruptions in adipose homeostasis plays a central cardiovascular physiology. We have previously shown that expression of the RNA binding protein HuR mediates energy expenditure, but potential impacts this finding not been explored. show here tissue-specific deletion (Adipo-HuR -/- ) is sufficient induce spontaneous development cardiac hypertrophy fibrosis. Hearts from Adipo-HuR mice increased left ventricular (LV) ejection fraction, rate pressure generation, LV posterior wall thickness accompanied by increase LV/body weight ratio hypertrophic gene expression. Furthermore, hearts display fibrosis picrosirius red staining periostin To identify underlying mechanisms, we applied both RNA-seq weighted co-expression network analysis (WGCNA) define HuR-dependent changes well significant relationships between mass. results demonstrate pro-inflammatory subcutaneous white (scWAT) serum levels TNF-α IL-6. WGCNA identified enrichment inflammation, apoptosis/cell death, vesicle-mediated transport genes among those whose most significantly associated with CVD . In conclusion, loss promotes fibrosis, potentially through modulation inflammation scWAT. NEW AND NOTEWORTHY This work demonstrates upon appears be mechanistically driven inflammatory extracellular vesicle mediating tissue. These suggest obesity, demonstrated mouse humans our group others, may contribute obesity-mediated CVD.

Language: Английский

HOXA5 Derives the Malignant Progression and Cisplatin Resistance of Esophageal Squamous Cell Carcinoma by Regulating USP18‐Mediated IFI27 Deubiquitination DOI Creative Commons
Qiang Wang, Shiheng Ren, Pan Zheng

et al.

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(4)

Published: Feb. 1, 2025

Chemo-resistance is a major obstacle to the treatment of esophageal squamous cell carcinoma (ESCC). Interferon alpha-inducible protein 27 (IFI27) has been reported be associated with ESCC progression. This study designed explore role and mechanism IFI27 in cisplatin (DDP) resistance ESCC. Ubiquitin-specific peptidase 18 (USP18) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). IFI27, multidrug resistance-associated 1 (MRP1), USP18, Homeobox A5 (HOXA5) determined using western blot. DDP resistance, viability, proliferation, apoptosis, invasion, migration assessed MTT, EdU, flow cytometry, transwell, wound healing. Interaction between USP18 was verified Co-immunoprecipitation (CoIP) assay. Binding HOXA5 promoter predicted JASPAR validated Chromatin immunoprecipitation (ChIP) dual-luciferase reporter assays. upregulated DDP-resistant tissues cells. knockdown repressed migration, induced apoptosis vitro. Mechanistically, deubiquitination prevented its degradation. Furthermore, transcription factor activated transcriptional activity via binding region. transcriptionally mediated could promote malignant behaviors through deubiquitinating providing promising therapeutic target for treatment.

Language: Английский

Citations

0

MxA suppresses TAK1-IKKα/β-NF-κB mediated inflammatory cytokine production to facilitate Mycobacterium tuberculosis infection DOI
Xinying Zhou, Lijie Zhang,

Linmiao Lie

et al.

Journal of Infection, Journal Year: 2020, Volume and Issue: 81(2), P. 231 - 241

Published: May 21, 2020

Language: Английский

Citations

22

Integrated Bioinformatics and Validation Reveal IFI27 and Its Related Molecules as Potential Identifying Genes in Liver Cirrhosis DOI Creative Commons

Zhiyu Xiong,

Ping Chen, Mengqin Yuan

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 14(1), P. 13 - 13

Published: Dec. 21, 2023

Liver cirrhosis remains a significant global public health concern, with liver transplantation standing as the foremost effective treatment currently available. Therefore, investigating pathogenesis of and developing novel therapies is imperative. Mitochondrial dysfunction stands out pivotal factor in its development. This study aimed to elucidate relationship between mitochondria using bioinformatic methods unveil pathogenesis. Initially, we identified 460 co-expressed differential genes (co-DEGs) from GSE14323 GSE25097 datasets, alongside their combined datasets. Functional analysis revealed that these co-DEGs were associated inflammatory cytokines cirrhosis-related signaling pathways. Utilizing weighted gene co-expression network (WCGNA), screened module genes, intersecting them oxidative stress-related mitochondrial genes. Two algorithms (least absolute shrinkage selection operator (LASSO) regression SVE-RFE) then employed further analyze Finally,

Language: Английский

Citations

7

Browning is activated in the subcutaneous white adipose tissue of mice metabolically challenged with a high-fructose diet submitted to high-intensity interval training DOI
Victor Faria Motta, Thereza Cristina Lonzetti Bargut, Vanessa Souza‐Mello

et al.

The Journal of Nutritional Biochemistry, Journal Year: 2019, Volume and Issue: 70, P. 164 - 173

Published: May 24, 2019

Language: Английский

Citations

11

Transcriptomic profiles of the ruminal wall in Italian Mediterranean dairy buffaloes fed green forage DOI Creative Commons
Angela Salzano, Salvatore Fioriniello, Nunzia D’Onofrio

et al.

BMC Genomics, Journal Year: 2023, Volume and Issue: 24(1)

Published: March 20, 2023

Abstract Background Green feed diet in ruminants exerts a beneficial effect on rumen metabolism and enhances the content of milk nutraceutical quality. At present, comprehensive analysis focused identification genes, therefore, biological processes modulated by green buffalo has never been reported. We performed RNA-sequencing buffaloes fed total mixed ration (TMR) + inclusion 30% ryegrass (treated) or TMR (control), identified differentially expressed genes (DEGs) using EdgeR NOISeq tools. Results found 155 DEGs ( p -values < 0.05) 61 (prob ≥0.8), 30 which are shared. The rt-qPCR validation suggested higher reliability results as compared with data, our context. Gene Ontology revealed that modulates relevant for physiology and, then, health well-being buffaloes, such lipid metabolism, response to oxidative stress, immune response, muscle structure function. Accordingly, we found: (i) up-regulation HSD17B13 , LOC102410803 (or PSAT1 ) HYKK down-regulation CDO1 SELENBP1 PEMT encoding factors involved energy, amino acid metabolism; (ii) enhanced expression SIM2 TRIM14 whose products implicated defense against infections, reduced LOC112585166 SAAL1 ), ROR2 SMOC2, S100A11 pro-inflammatory factors; (iii) NUDT18 DNAJA4 HSF4 counteract stressful conditions, LOC102396388 UGT1A9 LOC102413340 MRP4/ABCC4 detoxifying (iv) increased KCNK10, CACNG4, ATP2B4 proteins modulating Ca 2+ homeostasis, cytoskeleton - related MYH11 DES. Conclusion Although statistically unpowered, this study suggests functionality physiology, thus, welfare quality production Italian Mediterranean dairy buffaloes. These findings, need be further confirmed through additional DEGs, allow speculate role molecules, levels might also milk.

Language: Английский

Citations

4

Preliminary Single-Cell RNA-Sequencing Analysis Uncovers Adipocyte Heterogeneity in Lipedema DOI Creative Commons
Andrea Pagani, Dominik Duscher, Sally Kempa

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(12), P. 1028 - 1028

Published: June 13, 2024

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community with an intrinsic pathology that is difficult trace. The nature of lipedemic tissue one hypertrophic adipocytes poor turnover. So far, there are no identified pathways responsible, little known about cell populations fat. Methods: Adipose samples were collected from affected areas both healthy participants. For single-cell RNA sequencing analysis, dissociated into suspensions using enzymatic digestion then encapsulated nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted complementary DNA. Complementary DNA molecules amplified for downstream analysis. Results: RNA-sequencing analysis revealed three distinct adipocyte at play in lipedema. These have unique gene signatures which can characterized as lipid generating adipocyte, disease catalyst adipocyte. Conclusions: highlights triad subpopulations, functional roles. interplay between these subtypes offers promising insights complex pathophysiology

Language: Английский

Citations

1

The IFN-induced protein IFI27 binds MDA5 and counteracts its activation after SARS-CoV-2 infection DOI Creative Commons

Vanessa Rivero,

Julia Carrión-Cruz,

Darío López-García

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Oct. 4, 2024

Innate immune responses are induced after viral infections, being these essential to establish an antiviral response in the host. The RIG-I-like receptors (RLRs), RIG-I and MDA5 pivotal for virus detection by recognizing RNAs cytoplasm of infected cells, initiating responses. However, since excessive can have a negative effect on host, regulatory feedback mechanisms needed. In this work, we describe that IFN alpha-inducible protein 27 (IFI27) co-immunoprecipitates with melanoma differentiation-associated 5 (MDA5), interaction likely mediated RNAs. addition, using IFI27 overexpression, knock-out, knock-down show inhibits oligomerization activation, counteracting innate SARS-CoV-2 infections or polyinosinic-polycytidylic acid (poly(I:C)) transfection. Furthermore, our data indicate competes poly(I:C) binding, providing explanation inhibiting activation. This new function could be used design target-driven compounds treat diseases associated exacerbated induction responses, such as those SARS-CoV-2.

Language: Английский

Citations

1

Single-cell RNA-sequencing data analysis reveals a highly correlated triphasic transcriptional response to SARS-CoV-2 infection DOI Creative Commons
Pablo Andrés Gutiérrez Sánchez, Santiago F. Elena

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: Nov. 27, 2022

Abstract Single-cell RNA sequencing (scRNA-seq) is currently one of the most powerful techniques available to study transcriptional response thousands cells an external perturbation. Here, we perform a pseudotime analysis SARS-CoV-2 infection using publicly scRNA-seq data from human bronchial epithelial and colon ileum organoids. Our results reveal that, for genes, follows non-linear pattern characterized by initial final down-regulatory phase separated intermediate up-regulatory stage. A correlation profiles suggests common mechanism regulating mRNA levels genes. Interestingly, genes encoded in mitochondria or involved translation exhibited distinct profiles. To explain our results, propose simple model where nuclear export inhibition nsp1-sensitive transcripts will be sufficient shutdown infected cells.

Language: Английский

Citations

5

A IFI27 gene contributes to ER-stress mediated apoptosis and benefits for white spot syndrome virus infection in Litopenaeus vannamei DOI
Jin-Quan Fan,

Yu-Tao Miao,

Ke-Cheng Lu

et al.

Fish & Shellfish Immunology, Journal Year: 2021, Volume and Issue: 120, P. 180 - 189

Published: Nov. 25, 2021

Language: Английский

Citations

5

Maternal Western-style diet programs skeletal muscle gene expression in lean adolescent Japanese macaque offspring DOI Creative Commons
Emily A. Beck, Byron Hetrick, Luis R Nassar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 21, 2024

Early-life exposure to maternal obesity or a calorically dense Western-style diet (WSD) is strongly associated with greater risk of metabolic diseases in offspring, most notably insulin resistance and dysfunction-associated steatotic liver disease (MASLD). Prior studies our well-characterized Japanese macaque model demonstrated that offspring dams fed WSD, even when weaned onto control (CTR) diet, had reductions skeletal muscle mitochondrial metabolism increased compared on CTR diet. In the current study, we employed nested design test for differences gene expression from lean 3-year-old adolescent WSD both presence absence We included further account response post-weaning interaction effects between diets. Overall, found during pregnancy lactation was principal driver differential (DEG) at this time point. identified key pathways important signaling including PI3K-Akt MAP-kinase, regulation regeneration, transcription-translation feedback loops, male female offspring. Muscle DEG showed no measurable difference obese those WSD. A effected transcription only individuals group but not group. Collectively, identify composition has significant lasting impact transcriptome influences later transcriptional muscle, which may underlie

Language: Английский

Citations

0