Autophagy related 14 regulates liver homeostasis and function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1258151 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33409134_1.fastq.gz | Fastqsanger.gz | |||
| SRR33409134_2.fastq.gz | Fastqsanger.gz | |||
| SRR33409135_1.fastq.gz | Fastqsanger.gz | |||
| SRR33409135_2.fastq.gz | Fastqsanger.gz | |||
| SRR33409136_1.fastq.gz | Fastqsanger.gz |
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Project description:Autophagy regulated 14 (ATG14) is a key regulator of autophagy; however, its role in the liver remains poorly understood. This study aimed to investigate the hepatocyte-specific function of ATG14 in vivo. We generated Atg14 hepatocyte-specific knockout (HepKO) mice using adeno-associated virus (AAV) to deliver thyroxine-binding globulin (TBG) gene promoter-driven Cre into Atg14 floxed mice at an adult age and fed control and knockout mice with a Western diet for 4 weeks.
2025-05-07 | GSE296179 | GEO
Project description:Loss of muscle mass and function—a hallmark of skeletal muscle aging—is known as sarcopenia. Moreover, mammalian aging is reportedly driven by loss of epigenetic information. However, the effect of epigenetic alterations on skeletal muscle homeostasis is unknown. In this study, we show that chronic elevation of global DNA methylation results in a myopathy-like phenotype and age-related changes in skeletal muscle. Overexpression of muscle de novo methyltransferase 3a (Dnmt3a) increased central nucleus-positive myofibers, predominantly in fast-twitch myofibers, and shifted muscle fiber type to stress-resistant slow-twitch myofibers, accompanied by upregulation of chemokine and immune system-related genes and reduced basal autophagy in skeletal muscle. Dnmt3a overexpression reduced muscle androgen receptor signaling, decreased muscle mass and strength, and impaired tolerance to endurance exercise with age. Network analysis identified Akt1 as a potential hub gene. Dnmt3a expression reduced sensitivity to starvation-induced muscle atrophy by suppressing the FoxO-regulated autophagy and ubiquitin–proteasome systems. These data suggest that increased global DNA methylation disrupts skeletal muscle homeostasis, promotes age-related decline in muscle function, and reduces muscle plasticity.
2025-01-16 | GSE244432 | GEO
Project description:Autophagy is an essential mechanism involved in the degradation of cellular material and plays an important role in the maintenance of liver homeostasis. This study was designed to explore the effect of Autophagy-related 5 (Atg5) deficiency in liver CD11c+ cells in mice fed high-fat diet (HFD).
2021-12-15 | GSE190819 | GEO
Project description:Autophagy is essential for plant response to a variety of developmental and environmental factors. However, unlike yeast and animals, only a few autophagy genes in plants are functionally conserved in the biological world. An important question is, how plants form autophagy related functions in evolution? Here, we developed and verified a workflow that identified 997 high-confidence autophagy related genes (ARG) in A.thaliana using multi-group data from nearly 10,000 samples and established a co-network of autophagy containing 3,419 new presumptive connections. Of note, through the genomic analysis of 76 representative plants from lower to higher levels, we found that ARGs were preferentially retained after polyploidization followed by terrestrialization, forming plant-specific autophagy-related functions. In addition, we provide the evolutionary gains and losses of ARGs function in monocotyledons and dicotyledons, and verified two novel genes ml2 and ml5 presumed to be involved in autophagy and leaf senescence. This work provides valuable resources for the study of plant autophagy and highlights that ARGs may selectively promote the success of plant autophagy through polyploidy in the process of evolution.
2022-08-26 | GSE211896 | GEO
Project description:Accumulation of senescent cells affects organismal aging and the prevalence of age-associated disease. Emerging evidence suggests that activation of autophagy protects against age-associated diseases and promotes longevity, but the roles and regulatory mechanisms of autophagy in cellular senescence are not well understood. Here we identified the transcription factor, MondoA, as a novel regulator of cellular senescence, autophagy and mitochondrial homeostasis. MondoA protected against cellular senescence by activating autophagy partly through the suppression of an autophagy negative regulator, Rubicon. In addition, we identified peroxiredoxin 3 (Prdx3) as another downstream regulator of MondoA essential for mitochondrial homeostasis and autophagy. Rubicon and Prdx3 worked independently to regulate senescence. Furthermore, we found that MondoA knockout mice had exacerbated senescence during ischemic acute kidney injury (AKI), and a decrease of MondoA in the nucleus was correlated with human aging and ischemic AKI. Our results suggest that retaining MondoA activity protects from senescence and age-associated disease.
2022-03-01 | GSE179016 | GEO
Project description:Background: Autophagy plays an essential role in the occurrence and progression of Necrotizing enterocolitis (NEC). We purposed to carry out the identification and validation of the probable autophagy-related genes of NEC via bioinformatics methods and experiment trials. Methods: The autophagy-related differentially expressed genes (arDEGs) of NEC were identified by analyzing the RNA sequencing data of experiment neonatal mouse model and dataset GSE46619. Protein-protein interactions (PPI), gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used for the arDEGs. Then, co-expressed autophagy-related genes in two datasets were identified by Venn analysis and verified by qRT-PCR in experimental NEC. Results: Autophagy increased in experimental NEC and 47 arDEGs were identified in experimental NEC by RNA-sequencing. The PPI results proclaimed those genes interplayed with each other. The GO and KEGG enrichment results of arDEGs reported some certain enriched pathways related to autophagy and macroautophagy. Furthermore, 22 arDEGs were identified in human NEC from dataset GSE46619. The GO and KEGG enrichment analysis of these genes showed similar enriched terms with the results in experimental NEC. Finally, HIF-1a, VEGFA, ITGA3, ITGA6, ITGB4 and NAMPT were identified as co-expressed autophagy-related genes by Venn analysis in human NEC from dataset GSE46619 and experimental NEC. The result of qRT-PCR revealed the expression levels of HIF-1a and ITGA3 upregulated, VEGFA and ITGB4 downregulated in experimental NEC. Conclusion: We identified 47 arDEGs in experimental NEC and 22 arDEGs in human NEC via bioinformatics analysis. HIF-1a, ITGA3, VEGFA and ITGB4 may have effects on the progression of NEC through modulating autophagy.
2022-03-11 | GSE198372 | GEO
Project description:Age-related cell loss underpins many senescence-associated diseases. Senile cataract is a primary blindness-causing age-related ocular disease. Apoptosis of lens epithelial cells (LECs) is the common cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, the mechanism of which remains elusive. Here we reported the concomitance of increased autophagy and apoptosis in the same LEC from senile cataract patients. Oxidative stress triggered autophagy preceded apoptosis, while blocking autophagy by ablation of Atg7 or Atg3 gene remarkably suppressed apoptosis in HLE-B3 cell line. We identified autophagy adaptor SQSTM1/p62 as the critical scaffold protein to sustain a pro-survival signaling PKCι-NF-κB cascades, which antagonized the pro-apoptotic signaling in LECs. Importantly, prolonged autophagy in human senescent LECs responding to oxidative stress induced extensive degradation of p62 protein and therefore facilitated apoptosis. Moreover, pharmacological inhibitor of autophagy, 3-MA, significantly rescued apoptosis of human senescent LECs challenged by oxidative stress. Collectively, our data demonstrated that hyperactivation of autophagy aggravates age-related apoptotic cell death via inhibiting the p62-PKCι-NF-κB pro-survival axis in human senescent LECs. This work expands the understanding of the etiology of senile cataract and provides insight for mechanisms of age-related cell death in senescence-associated diseases.
2022-01-19 | GSE161701 | GEO
Project description:Axon integrity is crucial for neuronal function. To maintain axonal homeostasis neurons have evolved a unique organization of the microtubule (MT) cytoskeleton, which supports axonal morphology and provides tracks for intracellular transport. Although abnormal MT-based trafficking highlights the pathology of neurodegenerative diseases, the exact mechanism regulating MT dynamics in the axon remains enigmatic. Here we report on a novel regulation of MT dynamics by autophagy, the pathway, which previously has been linked to lysosomal degradation. We find that AuTophaGy(ATG)-related proteins required for LC3 lipid conjugation regulate MT stability via controlling the abundance of MT-binding protein CLASP2. This function of ATGs is independent of their role in protein degradation and requires the active zone protein ELKS1. Our results highlight a novel role of autophagy in neurons and suggest that pharmacological activation of autophagy may not only promote the degradation of bulk cytoplasmic material, but also impair axonal integrity via altering the MT stability.
2020-03-25 | PXD011279 | Pride
Project description:Autophagy is activated in pancreatic ductal adenocarcinoma (PDAC) and is currently being considered a promising therapeutic target in clinical trials. PDAC is a highly lethal disease with incidence rate equalling mortality rate. Main reasons for PDAC lethality are late-stage diagnosis, high agressiveness and metastatic rate, lack of effective treatments as well as specific diagnostic markers. Here we show that varying levels of the Autophagy related gene 5 (Atg5) determine pancreatic tumor formation and malignancy. While homozygous deletion of Atg5 blocks tumor progression in an in vivo model of PDAC, heterozygous deletion increases tumor aggressiveness and metastasis. Further analyses reveal that monoallelic loss of Atg5 affects mitochondrial homeostasis, changes intracellular calcium oscillations, heightens extracellular cathepsin activities , and promotes a pro-tumorigenic inflammatory microenvironment collectively enhancing tumor cell migration, invasion, and metastasis. Future treatments should take into account that variations in the autophagy pathway may have opposing effects on pancreatic tumor load, especially considering the multitude of autophagy inhibitors currently tested in clinical trials.
2018-10-15 | E-MTAB-6275 | biostudies-arrayexpress
Project description:In this study we provide data regarding sample charactheristics and genotypes in 150 human samples of European origin for SNPs located around genes related to metal homeostasis. SNPs were genotyped with the Illumina VeraCode technology (192-plex format). The genotyped SNPs were used to identify quantitative trait loci in the same samples. Data referring to the quantification of 18 micronutrients, the expression levels of 90 genes and the protein abundances of 40 proteins related to metal homeostasis in the same samples are directly available as supplementary material in the publication of this study.
| EGAS00001001292 | EGA